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US20160311772A1 - Compounds as tnik, ikkepsilon and tbk1 inhibitors and pharmaceutical composition comprising same - Google Patents

Compounds as tnik, ikkepsilon and tbk1 inhibitors and pharmaceutical composition comprising same Download PDF

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US20160311772A1
US20160311772A1 US15/134,987 US201615134987A US2016311772A1 US 20160311772 A1 US20160311772 A1 US 20160311772A1 US 201615134987 A US201615134987 A US 201615134987A US 2016311772 A1 US2016311772 A1 US 2016311772A1
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benzamide
amino
oxoisoindolin
oxo
isoindolin
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US9856216B2 (en
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Soongyu Choi
Eun-Jung Park
Hee Jeong Seo
Younggyu Kong
Ickhwan Son
Sang-Ho Ma
Man-Young Cha
Mi-Soon Kim
KiSoo Park
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GC Biopharma Corp
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Green Cross Corp Korea
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Assigned to GREEN CROSS CORPORATION reassignment GREEN CROSS CORPORATION ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: CHA, MAN-YOUNG, CHOI, SOONGYU, KIM, MI-SOON, KONG, YOUNGGYU, MA, SANG-HO, PARK, EUN-JUNG, PARK, KISOO, SEO, HEE JEONG, SON, ICKHWAN
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    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
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    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
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    • C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
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    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

Definitions

  • the present invention relates to novel compounds as TNIK (Traf2- and NCK-interacting kinase), IKK ⁇ (I-kappa-B kinase epsilon) and TBK1 (TANK-binding kinase 1) inhibitors and a pharmaceutical composition comprising same for the prevention or treatment of cancer.
  • TNIK Traf2- and NCK-interacting kinase
  • IKK ⁇ I-kappa-B kinase epsilon
  • TBK1 TANK-binding kinase 1
  • Cancer a genetic disorder caused by mutations of genes such as oncogene and tumor suppressor gene, is a serious life-threatening disease which is considered as 1 st or 2 nd ranked leading cause of death in humans.
  • various techniques have been developed for the treatment of cancer including surgical treatment, radiation therapy, immunotherapy, etc., problems related with inhibition and recurrence of malignant tumor still remain unresolved.
  • Protein kinase is a family of enzymes which plays an important role in signal transduction for various cellular activities including cellular proliferation, carcinogenesis, apoptosis, and cytodifferentiation, and it has been known that inhibitors thereof are useful in the treatment and prevention of proliferative diseases such as cancer (see Plowman, G. D, et al., Drug Discovery Today, 334-339 (1994)). In this regard, attempts have been made to treat proliferative diseases such as cancer by inhibiting protein kinase which is closely related with various signal transductions and disease mechanisms in cells.
  • IKK ⁇ and TBK1 are homoglous Ser/Thr kinases which play an essential role in the innate immune responses derived by induction of Type I interferon and other cytokines, and are activated by viral and bacterial infection.
  • the immune responses triggered by viral and bacterial infection include binding between Toll-like receptor and an antigen, e.g., lipopolysaccharide (LPS) or viral double-stranded RNA (dsRNA), followed by the activation of IKK ⁇ and/or TBK1 pathway.
  • LPS lipopolysaccharide
  • dsRNA viral double-stranded RNA
  • IRF7 IFN regulatory factor 7
  • IRF3 IFN regulatory factor 3
  • TNIK, IKK ⁇ and TBK1 are over-activated in patients with colon cancer, breast cancer, brain tumor, gastric cancer, hepatic cancer, ovarian cancer, and the like (see J. S. Boehm et al., Cell 129, 1065-1079, 2007).
  • Medications exhibiting inhibitory actions on TNIK, IKK ⁇ and TBK1 block signal transduction pathways of TNIK, IKK ⁇ and TBK1 by inhibiting phosphorylation of IRF3 and/or IRF7, which leads to the inhibition of angiogenesis, proliferation and survival of cancer, etc.
  • IRF3 and/or IRF7 phosphorylation of IRF3 and/or IRF7
  • TNIK, IKK ⁇ and TBK1 play an important role not only in basic processes of memory and learning via cellular signaling pathways, but also in the regulation of learning ability and judgment (see Takaoka et al., Drug Delivery Rev 60, 847-857, 2008). It is also expected that TNIK, IKK ⁇ and TBK1 inhibitors can be useful in the treatment and prevention of a wide range of diseases including inflammatory diseases as well as cancer.
  • It is another object of the present invention to provide a pharmaceutical composition comprising the compound for the prevention or treatment of cancer.
  • the present invention provides a compound of formula (I), a pharmaceutically acceptable salt, a hydrate, and a solvate thereof:
  • the present invention provides a pharmaceutical composition for the prevention or treatment of cancer, comprising the aforementioned compound and one or more pharmaceutically acceptable additives.
  • a compound in accordance with the present invention effectively inhibits TNIK, IKK ⁇ and TBK1, and thus is useful not only as an anticancer agent for the treatment of various cancers including colorectal cancer, breast cancer, CNS cancer, colon cancer, non-small cell lung cancer, kidney cancer, prostate cancer, ovarian cancer, uterus cancer, stomach cancer, liver cancer, skin cancer, lung cancer, brain cancer, bladder cancer, esophageal cancer, pancreatic cancer, thyroid cancer, head and neck cancer, squamous cell carcinoma, osteosarcoma, B-cell or T-cell lymphoma, acute or chronic leukemia and multiple myeloma, but as a therapeutic agent for chronic inflammation.
  • various cancers including colorectal cancer, breast cancer, CNS cancer, colon cancer, non-small cell lung cancer, kidney cancer, prostate cancer, ovarian cancer, uterus cancer, stomach cancer, liver cancer, skin cancer, lung cancer, brain cancer, bladder cancer, esophageal cancer, pancreatic cancer, thyroid cancer, head and
  • halogen refers to fluorine, chlorine, bromine or iodine, unless otherwise specified.
  • alkyl refers to linear or branched hydrocarbon chain radicals having 1 to 7 carbon atoms. Particular examples thereof may include, but not limited to, methyl, ethyl, N-propyl, i-propyl, N-butyl, i-butyl, t-butyl, N-pentyl, N-hexyl, and the like.
  • cycloalkyl refers to a saturated carbocyclic group having 3 to 10 carbon atoms which has a single ring (e.g., cyclohexyl) or a plurality of fused rings (e.g., norbornyl and adamantyl). Particular examples thereof may include, but not limited to, cyclopropyl, cyclopentyl, cyclohexyl, norbornyl, adamantyl, and the like.
  • aryl refers to an organic radical derived from aromatic hydrocarbon by removing one hydrogen therefrom, which includes a substituted or unsubstituted single ring or a plurality of fused rings, wherein each ring has 6 to 20, preferably, 6 to 14, atoms; it also includes a plurality of aryls which are connected via single bonds.
  • aryl also includes a fused bicyclic ring system, which comprises one benzene ring and one hetero ring containing nitrogen or oxygen atom. Particular examples thereof may include, but not limited to, phenyl, naphthyl, biphenyl, terphenyl, indenyl, isoindolinyl and the like.
  • the aryl group may be selected from phenyl, naphthyl, and the like.
  • heteroaryl refers to a 5- to 13-membered aromatic radical having at least one, preferably, 1 to 4, hetero atom selected from O, N and S; the heteroaryl includes monocyclic heteroaryl with 5- to 6-membered ring and polycyclic heteroaryl group condensed with at least one benzene ring; and the heteroaryl may be partially saturated. Also, in the present invention, the heteroaryl also includes a plurality of heteroaryls which are connected via single bonds. The heteroaryl group also includes heteroaryl in which the hetero atom in the ring is oxidized or forms a quaternary salt.
  • Particular examples may include, but not limited to, monocyclic heteroaryl such as furyl, thiophenyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, thiadiazolyl, isothiazolyl, isoxazolyl, oxazolyl, oxadizolyl, triazinyl, tetrazinyl, oxotriazolyl, tetrazolyl, furazanyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, and the like; polycyclic heteroaryl such as benzofuranyl, benzothiophenyl, dibenzofuranyl, dibenzothiophenyl, isobenzofuranyl, benzoimidazolyl, benzothiazolyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl, benzodioxoly
  • the heteroaryl is selected from the group consisting of thiophenyl, imidazolyl, pyrazolyl, thiazolyl, oxotriazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyridazinyl, benzothiophenyl, benzoimidazolyl, benzothiazolyl, benzothiadiazolyl, indolyl, indazolyl, quinolyl, isoquinolyl, benzodioxolyl, dihydrobenzofuranyl, dihydrobenzoxazinyl, benzodioxinyl, dihydrobenzodioxinyl, thioxothiazolidinyl, and the like.
  • heterocycloalkyl refers to 5- to 10-membered mono- or poly-cyclic ring, excluding aromatic ring, having at least one, preferably, 1 to 4, hetero atom selected from O, N and S.
  • Particular examples may include pyrrolidine, imidazoline, imidazolidine, pyrazoline, pyrazolidine, piperidine, morpholine, piperazine, tetrahydropyridinyl, and the like.
  • the present invention provides a compound selected from the group consisting of a compound of formula (I), a pharmaceutically acceptable salt, a hydrate, and a solvate thereof:
  • a compound in which X is CH, Y is CH 2 , and n is 1, has an oxoisoindoline scaffold and, thus, can be referred to as an ‘oxoisoindoline derivative’.
  • a compound in which X is CH, Y is CH 2 , and n is 2, has a 3,4-dihydroisoquinolin-1(2H)-one scaffold and, thus, can be referred to as a ‘3,4-dihydroisoquinolin-1 (2H)-one derivative’.
  • a compound in which X is CH, Y is C( ⁇ O), and n is 1, has a dioxoisoindoline scaffold and, thus, can be referred to as a ‘dioxoisoindoline derivative’.
  • a compound, in which X is N, Y is CH 2 , and n is 1, has a 1,2-dihydropyrrolo[3,4-c]pyridin-3-one scaffold and, thus, can be referred to as a ‘1,2-dihydropyrrolo[3,4-c]pyridin-3-one derivative’.
  • a compound in which X is N, Y is CH 2 , and n is 2, has a 3,4-dihydro-2,7-naphthyridin-1(2H)-one scaffold and, thus, can be referred to as a ‘3,4-dihydro-2,7-naphthyridin-1 (2H)-one derivative’.
  • a compound, in which X is N, Y is C( ⁇ O), and n is 1, has a 2H-pyrrolo[3,4-c]pyridin-1,3-dione scaffold and, thus, can be referred to as a ‘2H-pyrrolo[3,4-c]pyridin-1,3-dione derivative’.
  • the inventive compound may be an oxoisoindoline derivative having an oxoisoindoline scaffold.
  • R 1 is pyrrolidine.
  • R 1 is —NH—C( ⁇ O)—R 4 , R 4 being C 1-4 alkyl, substituted or unsubstituted phenyl, substituted or unsubstituted thiophenyl, substituted or unsubstituted furanyl, substituted or unsubstituted pyridinyl or substituted or unsubstituted pyrrolidinyl; and said phenyl, thiophenyl, furanyl, pyridinyl or pyrrolidinyl is optionally substituted with one or more substituents selected from the group consisting of fluoro, chloro, bromo, nitro, cyano, amino, tertbutyloxycarbonyl, methyl, methylthio, methylsulfonyl, methoxy, acetamido, methylpiperazinyl, aminopiperidinyl, morpholino, morpholinoethoxy, methylamino
  • R 1 is —NH—C( ⁇ O)—NH—R 5 , R 5 being methyl, ethyl, butyl, isopropyl, cyclopentyl, cyclohexyl or substituted or unsubstituted phenyl; and said phenyl is optionally substituted with one or more substituents selected from the group consisting of fluoro, chloro, cyano, nitro, methyl, methylthio and methoxy.
  • R 1 is —NH—C( ⁇ O)—O—R 6 , R 6 being phenyl.
  • R 1 is —NH—C( ⁇ S)—NH—R 7 , R 7 being phenyl.
  • R 1 is —NH—S( ⁇ O) 2 —R 8 , R 8 being phenyl, methyl, fluorophenyl or methoxyphenyl.
  • R 1 is —NH—R 9 -R 10 , R 9 being methyl, ethyl, propyl or butyl, and R 10 being H, hydroxy, chloro, cyano, methylamino, dimethylamino, phenyl, isoindolindione, methylpiperazinyl, piperidinyl, morpholino or pyrrolidine.
  • R 1 is —N(—R 11 )—R 12 , R 11 being methyl, and R 12 being methyl or butyl.
  • R 2 is substituted or unsubstituted phenyl, thiazolyl, pyrazolyl, imidazolyl, triazolyl, pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, pyrimidinyl, thiophenyl, furanyl, benzo[d]oxazol-7-yl, quinolinyl, indolyl, benzo[d]imidazolyl or benzofuranyl.
  • R 2 is selected from the group consisting of H; halogen; cyano; hydroxy; C 1-4 alkyl; C 3-5 cycloalkyl; phenyl unsubstituted or substituted with one or more substituents selected from the group consisting of hydroxy, cyano, amino, dimethylamino, ethyl, propyl, isopropyl, tertbutyl, acetyl, trifluoromethoxy, isopropoxy, methoxycarbonyl, methylthio, fluoro, methyl, chloro, methoxy, ethoxy, propoxy, butoxy, methylsulfonyl, —CF 3 , —O—CF 3 , and acetamido; thiazolyl; pyrazolyl; methylpyrazolyl; imidazolyl; methylimidazolyl; triazolyl; methyltriazolyl; pyridinyl; chloropyr
  • R 3 is methyl, —C( ⁇ O)—R 18 or —C( ⁇ O)—NH—R 19 , R 18 being furanyl or thiophenyl, and R 19 being cyclohexyl.
  • the inventive compound is selected from the group consisting of:
  • the compound according to the present invention may exist as a pharmaceutically acceptable salt.
  • the pharmaceutically acceptable salt of the inventive compound is a salt formed with an inorganic or organic acid.
  • the inorganic acid include hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, perchloric acid, bromic acid, and the like.
  • examples of the organic acid include acetic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, fumaric acid, maleic acid, malonic acid, phthalic acid, succinic acid, lactic acid, citric acid, gluconic acid, tartaric acid, salicylic acid, malic acid, oxalic acid, benzoic acid, embonic acid, aspartic acid, glutamic acid, and the like.
  • organic bases which can be used for preparing an organic base addition salt include tris(hydroxymethyl)methylamine, dicyclohexylamine, and the like.
  • Examples of amino acids which can be used for preparing an amino acid addition salt include natural amino acids such as alanine, glycine, and the like.
  • Said salts may be prepared by conventional methods known in the art, e.g., dissolving the compound of formula (I) in a water-miscible solvent such as methanol, ethanol, acetone, 1,4-dioxane, adding a free acid or free base thereto, and subjecting the mixture to crystallization.
  • a water-miscible solvent such as methanol, ethanol, acetone, 1,4-dioxane
  • the compounds of the present invention may have asymmetric carbon centers and, thus, may exist as R- or S-isomer, racemic mixtures, individual enantiomers or mixtures thereof, and individual diastereomers or mixtures thereof. Such stereoisomers and mixtures thereof are all included within the scope of the present invention.
  • solvates and hydrates of the compound of formula (I) are also included within the scope of the present invention.
  • Such solvates and hydrate may be prepared by conventional methods known in the art.
  • the solvates and hydrates are non-toxic and water-soluble, and form 1 to 5 bonds with water or alcohol-based solvent (particularly, ethanol and the like).
  • the present invention provides a pharmaceutical composition for the prevention or treatment of cancer, comprising a compound selected from the group consisting of the compound of formula (I), and a pharmaceutically acceptable salt, a hydrate and a solvate thereof.
  • cancers examples include colorectal cancer, breast cancer, CNS cancer, colon cancer, non-small cell lung cancer, kidney cancer, prostate cancer, ovarian cancer, uterus cancer, stomach cancer, liver cancer, skin cancer, lung cancer, brain cancer, bladder cancer, esophageal cancer, pancreatic cancer, thyroid cancer, head and neck cancer, squamous cell carcinoma, osteosarcoma, B-cell or T-cell lymphoma, acute or chronic leukemia and multiple myeloma.
  • inventive compound of formula (I) can inhibit TNIK, IKK ⁇ and TBK1, it can also be used for the prevention or treatment of diseases associated with TNIK, IKK ⁇ and TB protein activation, e.g., chronic inflammation, and the like.
  • a pharmaceutical composition of the present invention may comprise one or more conventional non-toxic pharmaceutically acceptable additives as effective components, in addition to the compound of formula (I) or a pharmaceutically acceptable salt, a hydrate or a solvate thereof.
  • acceptable additives for the pharmaceutical composition of the present invention include sweeteners, binders, solubilizing agents, dissolution aids, wetting agents, emulsifiers, isotonic agents, adsorbents, disintegrants, antioxidants, preservatives, lubricants, fillers, fragrances, and the like, e.g., lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, glycine, silica, talc, stearic acid, stearin, magnesium stearate, magnesium aluminum silicate, starch, gelatin, tragacanth gum, alginic acid, sodium alginate, methylcellulose, sodium carboxymethyl cellulose, agar, water, ethanol, polyethylene glycol, polyvinyl pyrrolidone, sodium chloride, calcium chloride, orange essence, strawberry essence, vanilla flavor, etc.
  • a pharmaceutical composition of the present invention may be prepared as an oral dosage form such as a tablet, a pill, powders, a capsule, a syrup or an emulsion or a parenteral dosage form for intramuscular, intravenous or subcutaneous administration.
  • the pharmaceutical composition is prepared in an oral dosage form.
  • the inventive pharmaceutical composition may contain additives such as cellulose, calcium silicate, corn starch, lactose, sucrose, dextrose, calcium phosphate, stearic acid, magnesium stearate, calcium stearate, gelatin, talc, a surfactant, a suspension agent, an emulsifier, a diluent, etc.
  • additives such as cellulose, calcium silicate, corn starch, lactose, sucrose, dextrose, calcium phosphate, stearic acid, magnesium stearate, calcium stearate, gelatin, talc, a surfactant, a suspension agent, an emulsifier, a diluent, etc.
  • the inventive pharmaceutical composition may contain additives such as water, brine, a glucose aqueous solution, an analog glucose aqueous solution, alcohol, glycol, ether, oil, a fatty acid, a fatty acid ester, a glyceride, a surfactant, a suspension agent, an emulsifier, etc.
  • additives such as water, brine, a glucose aqueous solution, an analog glucose aqueous solution, alcohol, glycol, ether, oil, a fatty acid, a fatty acid ester, a glyceride, a surfactant, a suspension agent, an emulsifier, etc.
  • a proposed daily dose of the compound in accordance with the present invention for an adult patient may be in the range of 0.1 to 2,000 mg/day.
  • the compound in accordance with the present invention may be administered in a single dose or in divided doses per day. It is understood that the daily dose should be determined in light of various relevant factors including health status, age, weight and sex of a subject to be treated, administration route and disease severity. Thus, the amount of proposed daily dose is not limited to the above-described range.
  • NMM N-methyl morpholine
  • BOP bis(2-oxo-3-oxazolidinyl)phosphinic chloride
  • DIPEA diisopropylethylamine
  • Microwave reaction was conducted with a Biotage InitiatorTM microwave synthesizer.
  • Mass spectra were obtained with either Quattro LC Triple Quadruple Tandem Mass Spectrometer (ESI; Micromass) or 1200LC/MSD (ESI; Agilent).
  • Step 1 Preparation of N-(3-oxo-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) isoindolin-4-yl)benzamide
  • Step 2 Preparation of (9H-fluoren-9-yl)methylmethyl(4-((3-oxo-7-phenylisoindolin-4-yl)carbamoyl)phenyl)carbamate (25)
  • Step 3 Preparation of 4-(methylamino)-N-(3-oxo-7-phenylisoindolin-4-yl) benzamide (26)

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Abstract

Provided is a compound of formula (I) as a TNIK (Traf2- and NCK-interacting kinase), IKKε (I-kappa-B kinase epsilon) and TBK1 (TANK-binding kinase 1) inhibitor; the compound according to the present invention effectively inhibits TNIK, IKKε and TBK1, and thus is useful not only as an anticancer agent for the treatment of various cancers including colorectal cancer, breast cancer, CNS cancer, colon cancer, non-small cell lung cancer, kidney cancer, prostate cancer, ovarian cancer, uterus cancer, stomach cancer, liver cancer, skin cancer, lung cancer, brain cancer, bladder cancer, esophageal cancer, pancreatic cancer, thyroid cancer, head and neck cancer, squamous cell carcinoma, osteosarcoma, B-cell or T-cell lymphoma, acute or chronic leukemia and multiple myeloma, but as a therapeutic agent for chronic inflammation.

Description

    FIELD OF THE INVENTION
  • The present invention relates to novel compounds as TNIK (Traf2- and NCK-interacting kinase), IKKε (I-kappa-B kinase epsilon) and TBK1 (TANK-binding kinase 1) inhibitors and a pharmaceutical composition comprising same for the prevention or treatment of cancer.
    • BACKGROUND OF THE INVENTION
  • Cancer, a genetic disorder caused by mutations of genes such as oncogene and tumor suppressor gene, is a serious life-threatening disease which is considered as 1st or 2nd ranked leading cause of death in humans. Although various techniques have been developed for the treatment of cancer including surgical treatment, radiation therapy, immunotherapy, etc., problems related with inhibition and recurrence of malignant tumor still remain unresolved.
  • Protein kinase is a family of enzymes which plays an important role in signal transduction for various cellular activities including cellular proliferation, carcinogenesis, apoptosis, and cytodifferentiation, and it has been known that inhibitors thereof are useful in the treatment and prevention of proliferative diseases such as cancer (see Plowman, G. D, et al., Drug Discovery Today, 334-339 (1994)). In this regard, attempts have been made to treat proliferative diseases such as cancer by inhibiting protein kinase which is closely related with various signal transductions and disease mechanisms in cells.
  • IKKε and TBK1 are homoglous Ser/Thr kinases which play an essential role in the innate immune responses derived by induction of Type I interferon and other cytokines, and are activated by viral and bacterial infection. The immune responses triggered by viral and bacterial infection include binding between Toll-like receptor and an antigen, e.g., lipopolysaccharide (LPS) or viral double-stranded RNA (dsRNA), followed by the activation of IKKε and/or TBK1 pathway. The activation of TBK1 and/or IKKε leads to phosphorylation of IFN regulatory factor 7 (IRF7) and/or IFN regulatory factor 3 (IRF3), which triggers dimerization and nuclear translocalization of interferon regulatory transcription factors, inducing signaling cascade that ultimately leads to the production of interferon (see Y.-H. Ou et al., Molecular Cell 41, 458-470, 2011 and D. A. Barbie et al., Nature, 1-5, 2009).
  • Recently, a study revealed that TNIK, IKKε and TBK1 are over-activated in patients with colon cancer, breast cancer, brain tumor, gastric cancer, hepatic cancer, ovarian cancer, and the like (see J. S. Boehm et al., Cell 129, 1065-1079, 2007). Medications exhibiting inhibitory actions on TNIK, IKKε and TBK1 block signal transduction pathways of TNIK, IKKε and TBK1 by inhibiting phosphorylation of IRF3 and/or IRF7, which leads to the inhibition of angiogenesis, proliferation and survival of cancer, etc. Thus, it is expected that such medications can be effectively used as therapeutic agents for the treatment of cancer (see WO2010-100431 and WO2009-030890).
  • Additionally, it is known that TNIK, IKKε and TBK1 play an important role not only in basic processes of memory and learning via cellular signaling pathways, but also in the regulation of learning ability and judgment (see Takaoka et al., Drug Delivery Rev 60, 847-857, 2008). It is also expected that TNIK, IKKε and TBK1 inhibitors can be useful in the treatment and prevention of a wide range of diseases including inflammatory diseases as well as cancer.
  • Conventionally, a number of TNIK, IKKε and TBK1 inhibitors have been developed, but such inhibitors have not yet been commercialized due to their poor effectiveness and deviations in therapeutic effects depending on the type of cancer. Thus, there is an increasing need for developing various compounds which are more effective in the treatment of cancer.
    • SUMMARY OF THE INVENTION
  • Therefore, it is an object of the present invention to provide compounds as TNIK, IKKε and TBK1 inhibitors.
  • Also, it is another object of the present invention to provide a pharmaceutical composition comprising the compound for the prevention or treatment of cancer.
  • In accordance with one object, the present invention provides a compound of formula (I), a pharmaceutically acceptable salt, a hydrate, and a solvate thereof:
  • Figure US20160311772A1-20161027-C00001
      • wherein,
      • X is CH or N;
      • Y is CH2 or C(═O);
      • n is 1 or 2;
      • R1 is 5- to 10-membered heterocycloalkyl, —NH2, —NH—C(═O)—R4, —NH—C(═O)—NH—R5, —NH—C(═O)—O—R6, —NH—C(═S)—NH—R7, —NH—S(═O)2—R8, —NH—R9-R10, or —N(—R11)—R12;
      • R2 is H, halogen, cyano, hydroxy, benzyl, C1-7 alkyl, substituted or unsubstituted C6-14 aryl, substituted or unsubstituted 5- to 13-membered heteroaryl, substituted or unsubstituted C3-10 cycloalkyl, —C(═O)—R13, —C(═O)—NH—R14, hydroxy-(C1-7 alkyl), —S—R15, —S(═O)2—R16 or —NH—R17; and
      • R3 is H, C1-7 alkyl, —C(═O)—R18 or —C(═O)—NH—R19;
      • wherein,
      • R4 to R8 are each independently C1-7 alkyl, substituted or unsubstituted C6-14 aryl, substituted or unsubstituted 5- to 13-membered heteroaryl, substituted or unsubstituted C3-10 cycloalkyl or substituted or unsubstituted 5- to 10-membered heterocycloalkyl;
      • R9 is C1-7 alkyl;
      • R10 is H, hydroxy, halogen, cyano, C1-7 alkyl, (C1-7 alkyl)amino, (diC1-7 alkyl)amino, substituted or unsubstituted C6-14 aryl, substituted or unsubstituted 5- to 13-membered heteroaryl or substituted or unsubstituted 5- to 10-membered heterocycloalkyl;
      • R11 and R12 are each independently C1-7 alkyl;
      • R13 and R14 are each independently hydroxy, C1-7 alkyl, or 5- to 10-membered heterocycloalkyl;
      • R15 to R17 are each independently substituted or unsubstituted C6-14 aryl or substituted or unsubstituted 5- to 13-membered heteroaryl;
      • R18 is 5- to 13-membered heteroaryl;
      • R19 is C3-10 cycloalkyl; and
      • said cycloalkyl, heterocycloalkyl, aryl or heteroaryl is optionally substituted with one or more substituents selected from the group consisting of C1-7 alkyl; —OCF3; C1-7 alkoxy; (C1-7 alkoxy)carbonyl; (C1-7 alkyl)carbonyl; C6-14 aryl; (C1-7 alkyl)thio; halogen; (C1-7 alkyl)sulfonyl; —NH—R20-R21; —N(CH3)—R20-R21; 5- to 13-membered heteroaryl; 5- to 10-membered heterocycloalkyl unsubstituted or substituted with C1-7 alkyl or amino; (C1-7 alkylcarbonylamino)(C6-14 aryl); (5- to 10-membered heterocycloalkyl)-(C1-7 alkyl)-(5- to 13-membered heteroaryl); —CF3; cyano; (C1-7 alkyl)amino; nitro; oxo; (5- to 10-membered heterocycloalkyl)-(C1-7 alkoxy); (diC1-7 alkyl)amino; (C1-7 alkyl)carbonylamino; hydroxy; (5- to 10-membered heterocycloalkyl)-(C1-7 alkyl); (tertbutoxycarbonyl)-(5- to 10-membered heterocycloalkyl)-(C1-7 alkyl); benzyl; and amino, wherein R20 is C6-14 aryl, 5- to 13-membered heteroaryl or C1-7 alkyl which is unsubstituted or substituted with hydroxy; and R21 is 5- to 10-membered heteroaryl or 5- to 10-membered heterocycloalkyl which is unsubstituted or substituted with H, hydroxy, halogen, amino, C1-7 alkyl, (diC1-7 alkyl)amino, C1-7 alkylcarbonylamino, C1-7 alkoxy, methyl or oxo.
  • In accordance with another object, the present invention provides a pharmaceutical composition for the prevention or treatment of cancer, comprising the aforementioned compound and one or more pharmaceutically acceptable additives.
  • A compound in accordance with the present invention effectively inhibits TNIK, IKKε and TBK1, and thus is useful not only as an anticancer agent for the treatment of various cancers including colorectal cancer, breast cancer, CNS cancer, colon cancer, non-small cell lung cancer, kidney cancer, prostate cancer, ovarian cancer, uterus cancer, stomach cancer, liver cancer, skin cancer, lung cancer, brain cancer, bladder cancer, esophageal cancer, pancreatic cancer, thyroid cancer, head and neck cancer, squamous cell carcinoma, osteosarcoma, B-cell or T-cell lymphoma, acute or chronic leukemia and multiple myeloma, but as a therapeutic agent for chronic inflammation.
    • DETAILED DESCRIPTION OF THE INVENTION
  • The term “halogen” as used herein, refers to fluorine, chlorine, bromine or iodine, unless otherwise specified.
  • The term “alkyl” as used herein, refers to linear or branched hydrocarbon chain radicals having 1 to 7 carbon atoms. Particular examples thereof may include, but not limited to, methyl, ethyl, N-propyl, i-propyl, N-butyl, i-butyl, t-butyl, N-pentyl, N-hexyl, and the like.
  • Also, the term “cycloalkyl” refers to a saturated carbocyclic group having 3 to 10 carbon atoms which has a single ring (e.g., cyclohexyl) or a plurality of fused rings (e.g., norbornyl and adamantyl). Particular examples thereof may include, but not limited to, cyclopropyl, cyclopentyl, cyclohexyl, norbornyl, adamantyl, and the like.
  • Also, the term “aryl” refers to an organic radical derived from aromatic hydrocarbon by removing one hydrogen therefrom, which includes a substituted or unsubstituted single ring or a plurality of fused rings, wherein each ring has 6 to 20, preferably, 6 to 14, atoms; it also includes a plurality of aryls which are connected via single bonds. In the present invention, aryl also includes a fused bicyclic ring system, which comprises one benzene ring and one hetero ring containing nitrogen or oxygen atom. Particular examples thereof may include, but not limited to, phenyl, naphthyl, biphenyl, terphenyl, indenyl, isoindolinyl and the like. Preferably, the aryl group may be selected from phenyl, naphthyl, and the like.
  • Also, the term “heteroaryl” refers to a 5- to 13-membered aromatic radical having at least one, preferably, 1 to 4, hetero atom selected from O, N and S; the heteroaryl includes monocyclic heteroaryl with 5- to 6-membered ring and polycyclic heteroaryl group condensed with at least one benzene ring; and the heteroaryl may be partially saturated. Also, in the present invention, the heteroaryl also includes a plurality of heteroaryls which are connected via single bonds. The heteroaryl group also includes heteroaryl in which the hetero atom in the ring is oxidized or forms a quaternary salt. Particular examples may include, but not limited to, monocyclic heteroaryl such as furyl, thiophenyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, thiadiazolyl, isothiazolyl, isoxazolyl, oxazolyl, oxadizolyl, triazinyl, tetrazinyl, oxotriazolyl, tetrazolyl, furazanyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, and the like; polycyclic heteroaryl such as benzofuranyl, benzothiophenyl, dibenzofuranyl, dibenzothiophenyl, isobenzofuranyl, benzoimidazolyl, benzothiazolyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl, benzodioxolyl, benzothiadiazolyl, dihydrobenzofuranyl, dihydrobenzoxazinyl, benzodioxinyl, dihydrobenzodioxinyl, thioxothiazolidinyl, isoindolyl, indolyl, indazolyl, quinolyl, isoquinolyl, cinnolinyl, quinazolinyl, quinoxalinyl, carbazolyl, phenanthridinyl, acridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxazinyl, and the like; N-oxides thereof (for example, pyridyl N-oxide and quinolyl N-oxide); and quaternary salts thereof. Preferably, the heteroaryl is selected from the group consisting of thiophenyl, imidazolyl, pyrazolyl, thiazolyl, oxotriazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyridazinyl, benzothiophenyl, benzoimidazolyl, benzothiazolyl, benzothiadiazolyl, indolyl, indazolyl, quinolyl, isoquinolyl, benzodioxolyl, dihydrobenzofuranyl, dihydrobenzoxazinyl, benzodioxinyl, dihydrobenzodioxinyl, thioxothiazolidinyl, and the like.
  • Also, the term “heterocycloalkyl” refers to 5- to 10-membered mono- or poly-cyclic ring, excluding aromatic ring, having at least one, preferably, 1 to 4, hetero atom selected from O, N and S. Particular examples may include pyrrolidine, imidazoline, imidazolidine, pyrazoline, pyrazolidine, piperidine, morpholine, piperazine, tetrahydropyridinyl, and the like.
  • The present invention provides a compound selected from the group consisting of a compound of formula (I), a pharmaceutically acceptable salt, a hydrate, and a solvate thereof:
  • Figure US20160311772A1-20161027-C00002
      • wherein,
      • X is CH or N;
      • Y is CH2 or C(═O);
      • n is 1 or 2;
      • R1 is 5- to 10-membered heterocycloalkyl, —NH2, —NH—C(═O)—R4, —NH—C(═O)—NH—R5, —NH—C(═O)—O—R6, —NH—C(═S)—NH—R7, —NH—S(═O)2—R8, —NH—R9-R10, or —N(—R11)—R12;
      • R2 is H, halogen, cyano, hydroxy, benzyl, C1-7 alkyl, substituted or unsubstituted C6-14 aryl, substituted or unsubstituted 5- to 13-membered heteroaryl, substituted or unsubstituted C3-10 cycloalkyl, —C(═O)—R13, —C(═O)—NH—R14, hydroxy-(C1-7 alkyl), —S—R15, —S(═O)2—R16 or —NH—R17; and
      • R3 is H, C1-7 alkyl, —C(═O)—R18 or —C(═O)—NH—R19;
      • wherein,
      • R4 to R8 are each independently C1-7 alkyl, substituted or unsubstituted C6-14 aryl, substituted or unsubstituted 5- to 13-membered heteroaryl, substituted or unsubstituted C3-10 cycloalkyl or substituted or unsubstituted 5- to 10-membered heterocycloalkyl;
      • R9 is C1-7 alkyl;
      • R10 is H, hydroxy, halogen, cyano, C1-7 alkyl, (C1-7 alkyl)amino, (diC1-7 alkyl)amino, substituted or unsubstituted C6-14 aryl, substituted or unsubstituted 5- to 13-membered heteroaryl or substituted or unsubstituted 5- to 10-membered heterocycloalkyl;
      • R11 and R12 are each independently C1-7 alkyl;
      • R13 and R14 are each independently hydroxy, C1-7 alkyl, or 5- to 10-membered heterocycloalkyl;
      • R15 to R17 are each independently substituted or unsubstituted C6-14 aryl or substituted or unsubstituted 5- to 13-membered heteroaryl;
      • R18 is 5- to 13-membered heteroaryl;
      • R19 is C3-10 cycloalkyl; and said cycloalkyl, heterocycloalkyl, aryl or heteroaryl is optionally substituted with one or more substituents selected from the group consisting of C1-7 alkyl; —OCF3; C1-7 alkoxy; (C1-7 alkoxy)carbonyl; (C1-7 alkyl)carbonyl; C6-14 aryl; (C1-7 alkyl)thio; halogen; (C1-7 alkyl)sulfonyl; —NH—R20-R21; —N(CH3)—R20-R21; 5- to 13-membered heteroaryl; 5- to 10-membered heterocycloalkyl unsubstituted or substituted with C1-7 alkyl or amino; (C1-7 alkylcarbonylamino)(C6-14 aryl); (5- to 10-membered heterocycloalkyl)-(C1-7 alkyl)-(5- to 13-membered heteroaryl); —CF3; cyano; (C1-7 alkyl)amino; nitro; oxo; (5- to 10-membered heterocycloalkyl)-(C1-7 alkoxy); (diC1-7 alkyl)amino; (C1-7 alkyl)carbonylamino; hydroxy; (5- to 10-membered heterocycloalkyl)-(C1-7 alkyl); (tertbutoxycarbonyl)-(5- to 10-membered heterocycloalkyl)-(C1-7 alkyl); benzyl; and amino, wherein R20 is C6-14 aryl, 5- to 13-membered heteroaryl or C1-7 alkyl which is unsubstituted or substituted with hydroxy; and R21 is 5- to 10-membered heteroaryl or 5- to 10-membered heterocycloalkyl which is unsubstituted or substituted with H, hydroxy, halogen, amino, C1-7 alkyl, (diC1-7 alkyl)amino, C1-7 alkylcarbonylamino, C1-7 alkoxy, methyl or oxo.
  • In formula (I), a compound, in which X is CH, Y is CH2, and n is 1, has an oxoisoindoline scaffold and, thus, can be referred to as an ‘oxoisoindoline derivative’.
  • In formula (I), a compound, in which X is CH, Y is CH2, and n is 2, has a 3,4-dihydroisoquinolin-1(2H)-one scaffold and, thus, can be referred to as a ‘3,4-dihydroisoquinolin-1 (2H)-one derivative’.
  • In formula (I), a compound, in which X is CH, Y is C(═O), and n is 1, has a dioxoisoindoline scaffold and, thus, can be referred to as a ‘dioxoisoindoline derivative’.
  • In formula (I), a compound, in which X is N, Y is CH2, and n is 1, has a 1,2-dihydropyrrolo[3,4-c]pyridin-3-one scaffold and, thus, can be referred to as a ‘1,2-dihydropyrrolo[3,4-c]pyridin-3-one derivative’.
  • In formula (I), a compound, in which X is N, Y is CH2, and n is 2, has a 3,4-dihydro-2,7-naphthyridin-1(2H)-one scaffold and, thus, can be referred to as a ‘3,4-dihydro-2,7-naphthyridin-1 (2H)-one derivative’.
  • In formula (I), a compound, in which X is N, Y is C(═O), and n is 1, has a 2H-pyrrolo[3,4-c]pyridin-1,3-dione scaffold and, thus, can be referred to as a ‘2H-pyrrolo[3,4-c]pyridin-1,3-dione derivative’.
  • Preferably, the inventive compound may be an oxoisoindoline derivative having an oxoisoindoline scaffold.
  • According to one embodiment of the present invention, R1 is pyrrolidine.
  • According to another embodiment of the present invention, R1 is —NH—C(═O)—R4, R4 being C1-4 alkyl, substituted or unsubstituted phenyl, substituted or unsubstituted thiophenyl, substituted or unsubstituted furanyl, substituted or unsubstituted pyridinyl or substituted or unsubstituted pyrrolidinyl; and said phenyl, thiophenyl, furanyl, pyridinyl or pyrrolidinyl is optionally substituted with one or more substituents selected from the group consisting of fluoro, chloro, bromo, nitro, cyano, amino, tertbutyloxycarbonyl, methyl, methylthio, methylsulfonyl, methoxy, acetamido, methylpiperazinyl, aminopiperidinyl, morpholino, morpholinoethoxy, methylamino, dimethylamino, dimethylaminoethylamino, dimethylaminopropylamino, aminoethylamino, hydroxyethylamino, hydroxypropylamino, hydroxybutylamino, methoxyethylamino, methoxypropylamino, methyl(2-(methylamino)ethyl)amino, acetamidoethylamino, pyrrolidinylethylamino, pyrrolidinylpropylamino, piperidinylethylamino, piperidinylpropylamino, azepanylethylamino, morpholinoethylamino, morpholinopropylamino, methylpiperazinylethylamino, methylpiperazinylpropylamino, thiophenylmethylamino, oxopyrrolidinylpropylamino, and (2-hydroxy-3-(piperidinyl)propyl)amino.
  • According to another embodiment of the present invention, R1 is —NH—C(═O)—NH—R5, R5 being methyl, ethyl, butyl, isopropyl, cyclopentyl, cyclohexyl or substituted or unsubstituted phenyl; and said phenyl is optionally substituted with one or more substituents selected from the group consisting of fluoro, chloro, cyano, nitro, methyl, methylthio and methoxy.
  • According to another embodiment of the present invention, R1 is —NH—C(═O)—O—R6, R6 being phenyl.
  • According to another embodiment of the present invention, R1 is —NH—C(═S)—NH—R7, R7 being phenyl.
  • According to another embodiment of the present invention, R1 is —NH—S(═O)2—R8, R8 being phenyl, methyl, fluorophenyl or methoxyphenyl.
  • According to another embodiment of the present invention, R1 is —NH—R9-R10, R9 being methyl, ethyl, propyl or butyl, and R10 being H, hydroxy, chloro, cyano, methylamino, dimethylamino, phenyl, isoindolindione, methylpiperazinyl, piperidinyl, morpholino or pyrrolidine.
  • According to another embodiment of the present invention, R1 is —N(—R11)—R12, R11 being methyl, and R12 being methyl or butyl.
  • According to one embodiment of the present invention, R2 is substituted or unsubstituted phenyl, thiazolyl, pyrazolyl, imidazolyl, triazolyl, pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, pyrimidinyl, thiophenyl, furanyl, benzo[d]oxazol-7-yl, quinolinyl, indolyl, benzo[d]imidazolyl or benzofuranyl.
  • According to another embodiment of the present invention, R2 is selected from the group consisting of H; halogen; cyano; hydroxy; C1-4 alkyl; C3-5 cycloalkyl; phenyl unsubstituted or substituted with one or more substituents selected from the group consisting of hydroxy, cyano, amino, dimethylamino, ethyl, propyl, isopropyl, tertbutyl, acetyl, trifluoromethoxy, isopropoxy, methoxycarbonyl, methylthio, fluoro, methyl, chloro, methoxy, ethoxy, propoxy, butoxy, methylsulfonyl, —CF3, —O—CF3, and acetamido; thiazolyl; pyrazolyl; methylpyrazolyl; imidazolyl; methylimidazolyl; triazolyl; methyltriazolyl; pyridinyl; chloropyridinyl; fluoropyridinyl; methoxyphenylaminopyridinyl; methoxypyridinyl; phenyl-1H-pyrrolo[2,3-b]pyridinyl; 1H-pyrrolo[2,3-b]pyridinyl; acetamidophenyl-1H-pyrrolo[2,3-b]pyridinyl; morpholinomethylthiophenyl-1H-pyrrolo[2,3-b]pyridinyl; pyrimidinyl; dichloropyrimidinyl; methoxyphenylaminopyrimidinyl; methylpyrazolylaminopyrimidinyl; phenylaminopyrimidinyl; fluorophenylaminopyrimidinyl; acetamidophenylaminopyrimidinyl; methylpiperazinylpyrimidinyl; morpholinopyrimidinyl; tolylaminopyrimidinyl; chloropyrimidinyl; thiophenyl; pyrrolidinylmethylthiophenyl; piperidinylmethylthiophenyl; morpholinomethylthiophenyl; tertbutyloxycarb onylpiperazinylmethylthiophenyl; furanyl; benzo[d]oxazol-7-yl; methyl-benzo[d]oxazol-7-yl; quinolinyl; indolyl; benzo[d]imidazolyl; benzofuranyl; —C(═O)—R13; —C(═O)—NH—R14; hydroxy-(C1-7 alkyl); —S—R15; —S(═O)2—R16; and —NH—R17; R13 being hydroxy, methoxy or pyrrolidinyl, R14 being methyl, R15 being phenyl, R16 being phenyl, and R17 being phenyl, methoxyphenyl, methylphenyl, fluorophenyl, chlorophenyl, dimethoxyphenyl, bis(trifluoromethyl)phenyl, dimethylphenyl, pyridinyl, pyrazinyl, methylpyrazolyl or pyrazolyl.
  • According to one embodiment of the present invention, R3 is methyl, —C(═O)—R18 or —C(═O)—NH—R19, R18 being furanyl or thiophenyl, and R19 being cyclohexyl.
  • According to preferred embodiments of the present invention, the inventive compound is selected from the group consisting of:
    • (1) N-(7-(2-ethylphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (2) N-(7-(3-isopropylphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (3) N-(7-(4-(tert-butyl)phenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (4) N-(3-oxo-7-(2-(trifluoromethoxy)phenyl)isoindolin-4-yl)benzamide;
    • (5) N-(3-oxo-7-(3-(trifluoromethoxy)phenyl)isoindolin-4-yl)benzamide;
    • (6) N-(7-(2-isopropoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (7) N-(7-(3-isopropoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (8) methyl 2-(7-benzamido-1-oxoisoindolin-4-yl)benzoate;
    • (9) methyl 3-(7-benzamido-1-oxoisoindolin-4-yl)benzoate;
    • (10) methyl 4-(7-benzamido-1-oxoisoindolin-4-yl)benzoate;
    • (11) N-(7-(2-acetylphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (12) N-(7-(3-acetylphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (13) N-(7-(4-acetylphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (14) N-(7-(2-(methylthio)phenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (15) N-(7-(2,4-difluorophenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (16) N-(7-(2,3-dimethylphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (17) N-(7-(2,3-dichlorophenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (18) N-(7-(2,4-dichlorophenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (19) N-(7-(2,5-dichlorophenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (20) N-(7-(3,4-dichlorophenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (21) N-(7-(3,5-dichlorophenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (22) N-(7-(4-fluoro-2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (23) N-(7-(2-chloro-3-fluorophenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (24) N-(7-(2-fluoro-3-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (25) N-(3-oxo-7-(2,3,4-trimethoxyphenyl)isoindolin-4-yl)benzamide;
    • (26) N-(7-(3,4-dimethylphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (27) N-(7-(3,5-dimethylphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (28) N-(7-(2,6-dimethylphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (29) N-(7-ethyl-3-oxoisoindolin-4-yl)benzamide;
    • (30) N-(7-(3,5-difluorophenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (31) N-(7-(2,5-dimethylphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (32) N-(7-(2,5-difluorophenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (33) N-(7-(3,4-difluorophenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (34) N-(7-(2,3-difluorophenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (35) N-(7-butyl-3-oxoisoindolin-4-yl)benzamide;
    • (36) 4-fluoro-N-(3-oxo-7-propylisoindolin-4-yl)benzamide;
    • (37) N-(7-methyl-3-oxoisoindolin-4-yl)benzamide;
    • (38) N-(7-(2,4-dimethylphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (39) N-(7-(4-ethylphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (40) N-(7-(4-isopropoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (41) N-(7-(4-(methylthio)phenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (42) N-(7-(3-ethylphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (43) N-(3-oxo-7-(2-propoxyphenyl)isoindolin-4-yl)benzamide;
    • (44) N-(3-oxo-7-(3-propoxyphenyl)isoindolin-4-yl)benzamide;
    • (45) N-(7-(2-butoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (46) N-(7-(3-butoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (47) N-(7-(2-(methylsulfonyl)phenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (48) N-(7-(3-fluoro-2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (49) N-(7-(4-chloro-2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (50) N-(7-(3-chloro-2-fluorophenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (51) N-(3-oxo-7-(thiazol-5-yl)isoindolin-4-yl)benzamide;
    • (52) N-(3-oxo-7-(thiazol-4-yl)isoindolin-4-yl)benzamide;
    • (53) N-(3-oxo-7-(thiazol-2-yl)isoindolin-4-yl)benzamide;
    • (54) N-(7-(1H-imidazol-4-yl)-3-oxoisoindolin-4-yl)benzamide;
    • (55) N-(3-oxo-7-(1H-pyrazol-4-yl)isoindolin-4-yl)benzamide;
    • (56) N-(7-(1-methyl-1H-imidazol-5-yl)-3-oxoisoindolin-4-yl)benzamide;
    • (57) N-(7-(1-methyl-1H-pyrazol-4-yl)-3-oxoisoindolin-4-yl)benzamide;
    • (58) N-(3-oxo-7-(1H-1,2,4-triazol-5-yl)isoindolin-4-yl)benzamide;
    • (59) N-(7-(1-methyl-1H-1,2,4-triazol-5-yl)-3-oxoisoindolin-4-yl)benzamide;
    • (60) 7-amino-4-(4-methoxyphenyl)isoindolin-1-one;
    • (61) 7-amino-4-(4-fluorophenyl)isoindolin-1-one;
    • (62) 7-amino-4-(4-chlorophenyl)isoindolin-1-one;
    • (63) 7-amino-4-(p-tolyl)isoindolin-1-one;
    • (64) 4-(4-acetylphenyl)-7-aminoisoindolin-1-one;
    • (65) 7-amino-4-(pyridin-4-yl)isoindolin-1-one;
    • (66) 7-amino-4-(2,6-dichloropyrimidin-4-yl)isoindolin-1-one;
    • (67) 7-amino-4-(2-chloropyrimidin-4-yl)isoindolin-1-one;
    • (68) 7-amino-4-(2-((3-methoxyphenyl)amino)pyridin-4-yl)isoindolin-1-one;
    • (69) 7-amino-4-(4-((3-methoxyphenyl)amino)pyridin-2-yl)isoindolin-1-one;
    • (70) 7-amino-4-(2-((3-methoxyphenyl)amino)pyrimidin-4-yl)isoindolin-1-one;
    • (71) 7-amino-4-(2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)isoindolin-1-one;
    • (72) 7-amino-4-(2-(phenylamino)pyrimidin-4-yl)isoindolin-1-one;
    • (73) 7-amino-4-(2-((3-fluorophenyl)amino)pyrimidin-4-yl)isoindolin-1-one;
    • (74) 7-amino-4-(2-((4-fluorophenyl)amino)pyrimidin-4-yl)isoindolin-1-one;
    • (75) 7-amino-4-(2-((4-methoxyphenyl)amino)pyrimidin-4-yl)isoindolin-1-one;
    • (76) N-(4-((4-(7-amino-1-oxoisoindolin-4-yl)pyrimidin-2-yl)amino)phenyl)acetamide;
    • (77) N-(3-((4-(7-amino-1-oxoisoindolin-4-yl)pyrimidin-2-yl)amino)phenyl)acetamide;
    • (78) 7-amino-4-(6-((3-methoxyphenyl)amino)pyrimidin-4-yl)isoindolin-1-one;
    • (79) 7-amino-4-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)isoindolin-1-one;
    • (80) 7-amino-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)isoindolin-1-one;
    • (81) 7-amino-4-(2-(4-methylpiperazin-1-yl)pyrimidin-4-yl)isoindolin-1-one;
    • (82) 7-amino-4-(2-morpholinopyrimidin-4-yl)isoindolin-1-one;
    • (83) 7-amino-4-(2-(p-tolylamino)pyrimidin-4-yl)isoindolin-1-one;
    • (84) 7-amino-4-(2-(m-tolylamino)pyrimidin-4-yl)isoindolin-1-one;
    • (85) N-(4-(3-(7-amino-1-oxoisoindolin-4-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)acetamide;
    • (86) 7-amino-4-(5-(5-(morpholinomethyl)thiophen-2-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)isoindolin-1-one;
    • (87) 2-methyl-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (88) 3-methyl-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (89) 4-methyl-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (90) 3-chloro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (91) 2,4-difluoro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (92) 3,4-difluoro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (93) 3,4-dimethyl-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (94) 2-(dimethylamino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (95) 3-(dimethylamino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (96) 2-(methylthio)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (97) 3-(methylthio)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (98) 2-(methylsulfonyl)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (99) 3-(methylsulfonyl)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (100) 4-(methylsulfonyl)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (101) 2,4-dimethoxy-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (102) 3,4-dimethoxy-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (103) 2,4-dichloro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (104) 3,4-dichloro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (105) 2,4-dimethyl-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (106) 2-acetamido-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (107) 3-acetamido-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (108) 4-(methylamino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (109) 3-methyl-N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide;
    • (110) 4-methyl-N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide;
    • (111) 5-methyl-N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide;
    • (112) N-(3-oxo-7-(o-tolyl)isoindolin-4-yl)benzamide;
    • (113) N-(3-oxo-7-(m-tolyl)isoindolin-4-yl)benzamide;
    • (114) N-(3-oxo-7-(2-(trifluoromethyl)phenyl)isoindolin-4-yl)benzamide;
    • (115) N-(3-oxo-7-(3-(trifluoromethyl)phenyl)isoindolin-4-yl)benzamide;
    • (116) 4-acetamido-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (117) N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (118) N-(7-(4-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (119) 4-nitro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (120) 4-acetamido-N-(7-(4-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (121) 4-methoxy-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (122) 4-fluoro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (123) N-(7-(4-fluorophenyl)-3-oxoisoindolin-4-yl)-4-methoxybenzamide;
    • (124) 4-acetamido-N-(7-(4-fluorophenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (125) N-(3-oxo-7-(thiophen-2-yl)isoindolin-4-yl)benzamide;
    • (126) N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)benzamide;
    • (127) N-(3-oxo-7-(pyridin-4-yl)isoindolin-4-yl)benzamide;
    • (128) N-(3-oxo-7-(pyridin-4-yl)isoindolin-4-yl)benzamide hydrochloride;
    • (129) 2-methoxy-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (130) 3-fluoro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (131) 4-(methylthio)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (132) N-(3-oxo-7-(4-propoxyphenyl)isoindolin-4-yl)benzamide;
    • (133) N-(7-(4-isopropylphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (134) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)furan-2-carboxamide;
    • (135) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-fluorobenzamide;
    • (136) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)thiophene-2-carboxamide;
    • (137) 4-fluoro-2-methyl-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (138) 4-acetamido-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (139) 4-(dimethylamino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (140) 4-acetamido-N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)benzamide;
    • (141) 4-fluoro-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (142) 2-fluoro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (143) 4-chloro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (144) N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (145) N-(7-(3-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (146) N-(3-oxo-7-(thiophen-3-yl)isoindolin-4-yl)benzamide;
    • (147) N-(7-(3-cyanophenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (148) N-(7-(3-(dimethylamino)phenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (149) N-(7-(2-fluorophenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (150) N-(7-(furan-3-yl)-3-oxoisoindolin-4-yl)benzamide;
    • (151) N-(7-(3-fluorophenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (152) N-(3-oxo-7-(pyridin-3-yl)isoindolin-4-yl)benzamide;
    • (153) N-(3-oxo-7-(pyridin-3-yl)isoindolin-4-yl)benzamide hydrochloride;
    • (154) N-(3-oxo-7-(pyrimidin-5-yl)isoindolin-4-yl)benzamide;
    • (155) 3-chloro-N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide;
    • (156) 5-bromo-N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide;
    • (157) 3-bromo-N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide;
    • (158) 4-fluoro-N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)benzamide;
    • (159) N-(3-oxo-7-phenylisoindolin-4-yl)pentanamide;
    • (160) N-(3-oxo-7-phenylisoindolin-4-yl)acetamide;
    • (161) N-(7-(2-chloropyrimidin-4-yl)-3-oxoisoindolin-4-yl)acetamide;
    • (162) N-(7-(2-((3-methoxyphenyl)amino)pyrimidin-4-yl)-3-oxoisoindolin-4-yl)acetamide;
    • (163) N-(7-(2-((3-fluorophenyl)amino)pyrimidin-4-yl)-3-oxoisoindolin-4-yl)acetamide;
    • (164) N-(3-oxo-7-(2-(m-tolylamino)pyrimidin-4-yl)isoindolin-4-yl)acetamide;
    • (165) N-(3-oxo-7-(2-(p-tolylamino)pyrimidin-4-yl)isoindolin-4-yl)acetamide;
    • (166) N-(7-(2-((3-methoxyphenyl)amino)pyrimidin-4-yl)-3-oxoisoindolin-4-yl)propionamide;
    • (167) N-(7-(4-(methylsulfonyl)phenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (168) N-(7-(3-(methylsulfonyl)phenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (169) N-(7-(3-acetamidophenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (170) 5-chloro-N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide;
    • (171) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (172) N-(7-(3,5-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (173) N-(7-cyclopropyl-3-oxoisoindolin-4-yl)benzamide;
    • (174) N-(7-(2-chlorophenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (175) N-(7-(2,4-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (176) N-(7-(3,4-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (177) N-(7-(3-ethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (178) N-(7-(2,5-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (179) N-(7-(4-chlorophenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (180) N-(7-(3-chlorophenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (181) N-(7-(4-ethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (182) N-(7-(2-ethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (183) N-(7-(2-cyanophenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (184) N-(7-(4-butoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (185) N-(7-(2-(dimethylamino)phenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (186) N-(3-oxo-7-(4-(trifluoromethoxy)phenyl)isoindolin-4-yl)benzamide;
    • (187) N-(7-(2,6-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (188) N-(3-oxo-7-(4-propylphenyl)isoindolin-4-yl)benzamide;
    • (189) N-(7-(2,3-dihydroxyphenyl)-3-oxoisoindolin-4-yl)-4-fluorobenzamide;
    • (190) 4-fluoro-N-(7-(2-hydroxy-3-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (191) 4-fluoro-N-(3-oxo-7-(thiophen-2-yl)isoindolin-4-yl)benzamide;
    • (192) 5-methyl-N-(3-oxo-7-phenylisoindolin-4-yl)furan-2-carboxamide;
    • (193) N-(7-(benzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)-4-fluorobenzamide;
    • (194) 4-fluoro-N-(7-(2-methylbenzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)benzamide;
    • (195) N-(3-oxo-7-(5-(pyrrolidin-1-ylmethyl)thiophen-2-yl)isoindolin-4-yl)benzamide;
    • (196) N-(3-oxo-7-(5-(piperidin-1-ylmethyl)thiophen-2-yl)isoindolin-4-yl)benzamide;
    • (197) N-(7-(5-(morpholinomethyl)thiophen-2-yl)-3-oxoisoindolin-4-yl)benzamide;
    • (198) tert-butyl 4-((5-(7-benzamido-1-oxoisoindolin-4-yl) thiophen-2-yl)methyl)piperazine-1-carboxylate;
    • (199) N-(7-(6-fluoropyridin-3-yl)-3-oxoisoindolin-4-yl)benzamide;
    • (200) N-(7-(6-methoxypyridin-3-yl)-3-oxoisoindolin-4-yl)benzamide;
    • (201) 2-chloro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (202) 3-methoxy-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (203) N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide;
    • (204) N-(7-(4-acetylphenyl)-3-oxoisoindolin-4-yl)-4-methoxybenzamide;
    • (205) N-(7-(4-fluorophenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (206) N-(7-(4-(dimethylamino)phenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (207) N-(7-(4-cyanophenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (208) 4-cyano-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (209) N-(3-oxo-7-(p-tolyl)isoindolin-4-yl)benzamide;
    • (210) N-(3-oxo-7-(4-(trifluoromethyl)phenyl)isoindolin-4-yl)benzamide;
    • (211) N-(3-oxo-7-phenylisoindolin-4-yl)isonicotinamide;
    • (212) N-(3-oxo-7-phenylisoindolin-4-yl)furan-2-carboxamide;
    • (213) N-(3-oxo-7-phenylisoindolin-4-yl)nicotinamide;
    • (214) 4-fluoro-N-(3-oxo-7-(quinolin-6-yl)isoindolin-4-yl)benzamide;
    • (215) 4-fluoro-N-(3-oxo-7-(quinolin-5-yl)isoindolin-4-yl)benzamide;
    • (216) 4-fluoro-N-(3-oxo-7-(quinolin-4-yl)isoindolin-4-yl)benzamide;
    • (217) N-(7-(1H-indol-7-yl)-3-oxoisoindolin-4-yl)-4-fluorobenzamide;
    • (218) N-(7-(1H-benzo[d]imidazol-4-yl)-3-oxoisoindolin-4-yl)-4-fluorobenzamide;
    • (219) N-(7-benzyl-3-oxoisoindolin-4-yl)-4-fluorobenzamide;
    • (220) (R)-tert-butyl 24-(3-oxo-7-phenylisoindolin-4-yl) carbamoyl)pyrrolidine-1-carboxylate;
    • (221) (R)—N-(3-oxo-7-phenylisoindolin-4-yl)pyrrolidine-2-carboxamide;
    • (222) 3-amino-N-(2-methyl-3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (223) 2-amino-N-(2-methyl-3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (224) N-(7-(2,3-dimethoxyphenyl)-2-(furan-2-carbonyl)-3-oxoisoindolin-4-yl) furan-2-carboxamide;
    • (225) N-(7-(2,3-dimethoxyphenyl)-3-oxo-2-(thiophene-2-carbonyl)isoindolin-4-yl)thiophene-2-carboxamide;
    • (226) 1-(4-fluorophenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea;
    • (227) 1-(3-oxo-7-phenylisoindolin-4-yl)-3-phenylurea;
    • (228) 1-(4-cyanophenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea;
    • (229) 1-butyl-3-(3-oxo-7-phenylisoindolin-4-yl)urea;
    • (230) 1-(4-methoxyphenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea;
    • (231) 1-cyclohexyl-3-(3-oxo-7-phenylisoindolin-4-yl)urea;
    • (232) 1-(3-oxo-7-phenylisoindolin-4-yl)-3-(p-tolyl)urea;
    • (233) 1-(2-methoxyphenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea;
    • (234) 1-isopropyl-3-(3-oxo-7-phenylisoindolin-4-yl)urea;
    • (235) 1-(4-nitrophenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea;
    • (236) 1-ethyl-3-(3-oxo-7-phenylisoindolin-4-yl)urea;
    • (237) 1-(4-acetylphenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea;
    • (238) 1-(3-oxo-7-phenylisoindolin-4-yl)-3-(o-tolyl)urea;
    • (239) 1-cyclopentyl-3-(3-oxo-7-phenylisoindolin-4-yl)urea;
    • (240) 1-(3-fluorophenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea;
    • (241) 1-(3-(methylthio)phenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea;
    • (242) 1-(2-fluorophenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea;
    • (243) 1-(4-chlorophenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea;
    • (244) 1-(7-(4-methoxyphenyl)-3-oxoisoindolin-4-yl)-3-phenylurea;
    • (245) 1-(7-(4-fluorophenyl)-3-oxoisoindolin-4-yl)-3-phenylurea;
    • (246) 7-amino-N-cyclohexyl-1-oxo-4-phenylisoindolin-2-carboxamide;
    • (247) 1-(3-oxo-7-phenylisoindolin-4-yl)-3-phenylthiourea;
    • (248) phenyl (3-oxo-7-phenylisoindolin-4-yl)carbamate;
    • (249) N-(3-oxo-7-phenylisoindolin-4-yl)benzenesulfonamide;
    • (250) N-(3-oxo-7-phenylisoindolin-4-yl)methanesulfonamide;
    • (251) 4-fluoro-N-(3-oxo-7-phenylisoindolin-4-yl)benzenesulfonamide;
    • (252) 4-methoxy-N-(3-oxo-7-phenylisoindolin-4-yl)benzenesulfonamide;
    • (253) 7-((2-chloroethyl)amino)-4-phenylisoindolin-1-one;
    • (254) 3-((3-oxo-7-phenylisoindolin-4-yl)amino)propanenitrile;
    • (255) 7-((2-(dimethylamino)ethyl)amino)-4-phenylisoindolin-1-one;
    • (256) 7-((2-hydroxyethyl)amino)-4-phenylisoindolin-1-one;
    • (257) 2-(2-((3-oxo-7-phenylisoindolin-4-yl)amino)ethyl)isoindolin-1,3-dione;
    • (258) 7-((2-(4-methylpiperazin-1-yl)ethyl)amino)-4-phenylisoindolin-1-one;
    • (259) 4-phenyl-7-((2-(piperidin-1-yl)ethyl)amino)isoindolin-1-one;
    • (260) 7-((2-morpholinoethyl)amino)-4-phenylisoindolin-1-one;
    • (261) 7-((2-(methylamino)ethyl)amino)-4-phenylisoindolin-1-one;
    • (262) 4-phenyl-7-((2-(pyrrolidin-1-yl)ethyl)amino)isoindolin-1-one;
    • (263) 7-(benzylamino)-4-phenylisoindolin-1-one;
    • (264) 2-(3-((3-oxo-7-phenylisoindolin-4-yl)amino)propyl)isoindolin-1,3-dione;
    • (265) 4-(pyridin-4-yl)-7-(pyrrolidin-1-yl)isoindolin-1-one;
    • (266) 7-(dimethylamino)-4-(2-((3-methoxyphenyl)amino)pyrimidin-4-yl) isoindolin-1-one;
    • (267) 7-(dimethylamino)-4-(2-((3-fluorophenyl)amino)pyrimidin-4-yl) isoindolin-1-one;
    • (268) 7-(butylamino)-4-(2-((3-methoxyphenyl)amino)pyrimidin-4-yl) isoindolin-1-one;
    • (269) 7-(butyl(methyl)amino)-4-(2-((3-methoxyphenyl)amino)pyrimidin-4-yl) isoindolin-1-one;
    • (270) 7-(butyl(methyl)amino)-4-(2-((3-methoxyphenyl)amino)pyrimidin-4-yl)-2-methylisoindolin-1-one;
    • (271) 4-amino-7-phenylisoindolin-1,3-dione;
    • (272) 4-amino-7-(2-methoxyphenyl)isoindolin-1,3-dione;
    • (273) 4-amino-7-(2,3-dimethoxyphenyl)isoindolin-1,3-dione;
    • (274) 4-amino-7-(furan-2-yl)isoindolin-1,3-dione;
    • (275) 4-amino-7-(thiophen-2-yl)isoindolin-1,3-dione;
    • (276) N-(1,3-dioxo-7-phenylisoindolin-4-yl)benzamide;
    • (277) N-(7-(2-methoxyphenyl)-1,3-dioxoisoindolin-4-yl)benzamide;
    • (278) N-(7-(2,3-dimethoxyphenyl)-1,3-dioxoisoindolin-4-yl)benzamide;
    • (279) 4-fluoro-N-(3-oxo-7-phenyl-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yl) benzamide;
    • (280) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl) propyl)amino)benzamide;
    • (281) N-(7-bromo-3-oxoisoindolin-4-yl)-4-((2-(dimethylamino)ethyl)amino) benzamide;
    • (282) N-(7-bromo-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl) propyl)amino) benzamide;
    • (283) N-(7-bromo-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino) benzamide;
    • (284) N-(7-bromo-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino) benzamide;
    • (285) 4-((2-(azepan-1-yl)ethyl)amino)-N-(7-bromo-3-oxoisoindolin-4-yl) benzamide;
    • (286) N-(7-bromo-3-oxoisoindolin-4-yl)-4-((3-(dimethylamino)propyl)amino) benzamide;
    • (287) N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl) amino)benzamide;
    • (288) N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((2-methoxyethyl)amino) benzamide;
    • (289) N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino) benzamide;
    • (290) N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((2-morpholinoethyl)amino) benzamide;
    • (291) 4-((2-(dimethylamino)ethyl)amino)-N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)benzamide;
    • (292) N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((2-hydroxyethyl)amino) benzamide;
    • (293) 4-((2-(azepan-1-yl)ethyl)amino)-N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)benzamide;
    • (294) N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((2-(4-methylpiperazin-1-yl)ethyl)amino)benz amide;
    • (295) N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((3-(4-methylpiperazin-1-yl)propyl)amino)benzamide;
    • (296) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-morpholinopropyl)amino)benz amide;
    • (297) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-morpholinoethyl)amino)benzamide;
    • (298) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide;
    • (299) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
    • (300) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-methoxyethyl)amino)benzamide;
    • (301) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(dimethylamino)ethyl)amino)benzamide;
    • (302) N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide;
    • (303) N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide hydrochloride;
    • (304) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide hydrochloride;
    • (305) 4-((2-(dimethylamino)ethyl)amino)-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (306) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-(dimethylamino)propyl)amino) benzamide;
    • (307) N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benz amide;
    • (308) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide;
    • (309) 2-methyl-N-(3-oxo-7-phenylisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
    • (310) 4-((3-methoxypropyl)amino)-N-(7-(2-methoxypyridin-3-yl)-3-oxoisoindolin-4-yl)benzamide;
    • (311) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-hydroxyethyl)amino)benzamide;
    • (312) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-morpholinobenzamide;
    • (313) N-(7-(3-fluoro-2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
    • (314) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(4-methylpiperazin-1-yl)ethyl) amino)benzamide;
    • (315) 4-((2-aminoethyl)amino)-N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (316) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-(4-methylpiperazin-1-yl)propyl)amino)benzamide;
    • (317) N-(3-oxo-7-phenylisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
    • (318) N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
    • (319) 4-(4-methylpiperazin-1-yl)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (320) 4-morpholino-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (321) 4-((2-methoxyethyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (322) 4-((2-morpholinoethyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (323) N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-morpholinobenzamide;
    • (324) 4-((2-methoxyethyl)amino)-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (325) N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-(4-methylpiperazin-1-yl)benzamide;
    • (326) N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-morpholinoethyl)amino)benzamide;
    • (327) 4-((3-morpholinopropyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (328) N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-morpholinopropyl)amino)benzamide;
    • (329) 4-((3-(4-methylpiperazin-1-yl)propyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (330) N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-(4-methylpiperazin-1-yl)propyl)amino)benzamide;
    • (331) 4-((3-methoxypropyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (332) N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-methoxypropyl)amino)benzamide;
    • (333) N-(3-oxo-7-phenylisoindolin-4-yl)-4-((thiophen-2-ylmethyl)amino)benzamide;
    • (334) N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((thiophen-2-ylmethyl)amino)benzamide;
    • (335) 4-((3-(dimethylamino)propyl)amino)-N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)benzamide
    • (336) N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((3-methoxypropyl)amino)benzamide;
    • (337) N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((3-morpholinopropyl)amino)benzamide;
    • (338) N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide;
    • (339) N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide;
    • (340) 4-(4-aminopiperidin-1-yl)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (341) N-(7-(benzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)-4-((2-(dimethylamino)ethyl)amino)benzamide;
    • (342) N-(7-(benzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide;
    • (343) N-(7-(benzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide;
    • (344) 4-((2-(azepan-1-yl)ethyl)amino)-N-(7-(benzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)benzamide;
    • (345) 4-(2-morpholinoethoxy)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (346) N-(3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
    • (347) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-(2-morpholinoethoxy)benzamide;
    • (348) N-(7-(3-amino-2-hydroxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-morpholinoethyl)amino)benzamide;
    • (349) 4-((2-(azepan-1-yl)ethyl)amino)-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (350) 4-((2-(azepan-1-yl)ethyl)amino)-N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (351) 4-((3-(dimethylamino)propyl)amino)-N-(7-(2-hydroxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (352) 4-((2-hydroxyethyl)amino)-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (353) 4-((2-hydroxyethyl)amino)-N-(7-(2-hydroxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (354) 4-((3-hydroxypropyl)amino)-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (355) N-(7-(2-hydroxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-hydroxypropyl)amino)benzamide;
    • (356) 4-((4-hydroxybutyl)amino)-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (357) 4-((4-hydroxybutyl)amino)-N-(7-(2-hydroxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
    • (358) 4-(methyl(2-(methylamino)ethyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (359) N-(7-(2,3-difluorophenyl)-3-oxoisoindolin-4-yl)-4-((2-morpholinoethyl)amino)benzamide;
    • (360) N-(3-oxo-7-phenylisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide;
    • (361) N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide;
    • (362) 4-((2-(dimethylamino)ethyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (363) N-(3-oxo-7-phenylisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide;
    • (364) N-(7-(2,3-difluorophenyl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
    • (365) N-(7-(2,3-difluorophenyl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide hydrochloride;
    • (366) N-(7-(2,3-difluorophenyl)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide hydrochloride;
    • (367) N-(7-(2,3-difluorophenyl)-3-oxoisoindolin-4-yl)-4-((2-(dimethylamino)ethyl)amino)benzamide;
    • (368) N-(7-(2,3-difluorophenyl)-3-oxoisoindolin-4-yl)-4-((3-(dimethylamino)propyl)amino)benzamide;
    • (369) 4-((2-(azepan-1-yl)ethyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (370) N-(3-oxo-7-phenylisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide;
    • (371) 4-((2-hydroxyethyl)amino)-N-(3-oxo-7-(thiophen-2-yl)isoindolin-4-yl)benzamide;
    • (372) 4-((2-methoxyethyl)amino)-N-(3-oxo-7-(thiophen-2-yl)isoindolin-4-yl)benzamide;
    • (373) 4-((2-(dimethylamino)ethyl)amino)-N-(3-oxo-7-(thiophen-2-yl)isoindolin-4-yl)benzamide;
    • (374) N-(3-oxo-7-(thiophen-2-yl)isoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide;
    • (375) 4-((2-morpholinoethyl)amino)-N-(3-oxo-7-(thiophen-2-yl)isoindolin-4-yl)benzamide;
    • (376) N-(7-(benzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
    • (377) N-(7-(2-methylbenzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl) amino)benzamide;
    • (378) 4-((2-(4-methylpiperazin-1-yl)ethyl)amino)-N-(3-oxo-7-(thiophen-2-yl)isoindolin-4-yl)benzamide;
    • (379) 4-((2-(4-methylpiperazin-1-yl)ethyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (380) 4-((2-hydroxyethyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (381) 4-((3-(dimethylamino)propyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (382) 4-((3-hydroxypropyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (383) 4-((4-hydroxybutyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
    • (384) N-(7-(benzofuran-2-yl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
    • (385) N-(3-oxo-7-(quinolin-6-yl)isoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
    • (386) N-(3-oxo-7-(quinolin-5-yl)isoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
    • (387) N-(3-oxo-7-(quinolin-4-yl)isoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
    • (388) 7-(4-fluorobenzamido)-1-oxoisoindoline-4-carboxylic acid;
    • (389) 7-(4-fluorobenzamido)-N-methyl-1-oxoisoindoline-4-carboxamide;
    • (390) N-methyl-1-oxo-7-(4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamido)isoindoline-4-carboxamide;
    • (391) 4-fluoro-N-(3-oxo-7-(pyrrolidine-1-carbonyl)isoindolin-4-yl)benzamide;
    • (392) N-(3-oxo-7-(pyrrolidine-1-carbonyl)isoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino) benzamide;
    • (393) 4-fluoro-N-(7-(2-hydroxypropan-2-yl)-3-oxoisoindolin-4-yl)benzamide;
    • (394) N-(7-(2-hydroxypropan-2-yl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino) benzamide;
    • (395) N-(7-cyano-3-oxoisoindolin-4-yl)-4-fluorobenzamide;
    • (396) 4-fluoro-N-(7-hydroxy-3-oxoisoindolin-4-yl)benzamide;
    • (397) 4-acetamido-N-(1-oxo-5-phenyl-1,2,3,4-tetrahydroisoquinolin-8-yl)benzamide;
    • (398) N-(1-oxo-5-phenyl-1,2,3,4-tetrahydroisoquinolin-8-yl)benzamide;
    • (399) N-(1-oxo-5-phenyl-1,2,3,4-tetrahydroisoquinolin-8-yl)furan-2-carboxamide;
    • (400) N-(5-(2,3-dimethoxyphenyl)-1-oxo-1,2,3,4-tetrahydroisoquinolin-8-yl)-4-fluorobenzamide;
    • (401) N-(1-oxo-5-phenyl-1,2,3,4-tetrahydroisoquinolin-8-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
    • (402) N-(5-(2-methoxyphenyl)-1-oxo-1,2,3,4-tetrahydroisoquinolin-8-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
    • (403) N-(5-bromo-1-oxo-1,2,3,4-tetrahydroisoquinolin-8-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
    • (404) 4-fluoro-N-(3-oxo-7-(phenylthio)isoindolin-4-yl)benzamide;
    • (405) N-(1-oxo-5-(phenylthio)-1,2,3,4-tetrahydroisoquinolin-8-yl)-4-((2-(pyrrolidin-1-yl)ethyl) amino)benzamide;
    • (406) N-(3-oxo-7-(phenylsulfonyl)isoindolin-4-yl)benzamide;
    • (407) N-(3-oxo-7-(phenylthio)isoindolin-4-yl)benzamide;
    • (408) 4-fluoro-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
    • (409) N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
    • (410) N-(7-((2-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)benzamide;
    • (411) N-(3-oxo-7-(o-tolylamino)isoindolin-4-yl)benzamide;
    • (412) N-(3-oxo-7-(p-tolylamino)isoindolin-4-yl)benzamide;
    • (413) N-(7-((2-fluorophenyl)amino)-3-oxoisoindolin-4-yl)benzamide;
    • (414) N-(7-((4-fluorophenyl)amino)-3-oxoisoindolin-4-yl)benzamide;
    • (415) N-(7-((3-fluorophenyl)amino)-3-oxoisoindolin-4-yl)benzamide;
    • (416) N-(7-((4-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)benzamide;
    • (417) 4-methyl-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
    • (418) N-(7-((3-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-fluorobenzamide;
    • (419) N-(7-((2-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-fluorobenzamide;
    • (420) 2-fluoro-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
    • (421) 3-fluoro-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
    • (422) N-(7-((2,3-dimethoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-fluorobenzamide;
    • (423) N-(7-((3,5-bis(trifluoromethyl)phenyl)amino)-3-oxoisoindolin-4-yl)-4-fluorobenzamide;
    • (424) N-(7-((2,3-dimethylphenyl)amino)-3-oxoisoindolin-4-yl)-4-fluorobenzamide;
    • (425) 4-fluoro-N-(7-((2-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)benzamide;
    • (426) 4-fluoro-N-(3-oxo-7-(o-tolylamino)isoindolin-4-yl)benzamide;
    • (427) 4-fluoro-N-(3-oxo-7-(pyridin-3-ylamino)isoindolin-4-yl)benzamide;
    • (428) 4-fluoro-N-(3-oxo-7-(pyridin-2-ylamino)isoindolin-4-yl)benzamide;
    • (429) 4-fluoro-N-(3-oxo-7-(pyrazin-2-ylamino)isoindolin-4-yl)benzamide;
    • (430) 4-fluoro-N-(7-((1-methyl-1H-pyrazol-4-yl)amino)-3-oxoisoindolin-4-yl)benzamide;
    • (431) N-(7-((3-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)benzamide;
    • (432) 2-methoxy-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
    • (433) 4-methoxy-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
    • (434) 3-methoxy-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
    • (435) 4-acetamido-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
    • (436) N-(3-oxo-7-(m-tolylamino)isoindolin-4-yl)benzamide;
    • (437) N-(7-((1H-pyrazol-3-yl)amino)-3-oxoisoindolin-4-yl)-4-fluorobenzamide;
    • (438) N-(3-oxo-7-(phenylamino)isoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
    • (439) N-(3-oxo-7-(phenylamino)isoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide;
    • (440) N-(3-oxo-7-(phenylamino)isoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide hydrochloride;
    • (441) 4-((2-(dimethylamino)ethyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
    • (442) 4-((2-morpholinoethyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
    • (443) 4-((2-(4-methylpiperazin-1-yl)ethyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
    • (444) 4-((2-methoxyethyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
    • (445) N-(7-((3-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
    • (446) N-(7-((3-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide;
    • (447) N-(7-((3-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide;
    • (448) N-(7-((3-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide;
    • (449) N-(3-oxo-7-(m-tolylamino)isoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
    • (450) N-(3-oxo-7-(m-tolylamino)isoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide;
    • (451) N-(3-oxo-7-(m-tolylamino)isoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide;
    • (452) N-(3-oxo-7-(m-tolylamino)isoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide;
    • (453) N-(7-((2-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino) benzamide;
    • (454) N-(7-((2-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino) benzamide;
    • (455) N-(7-((3-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino) benzamide;
    • (456) N-(7-((3-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino) benzamide;
    • (457) N-(7-((3-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide;
    • (458) N-(7-((3-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide;
    • (459) N-(3-oxo-7-(phenylamino)isoindolin-4-yl)-4-((3-(2-oxopyrrolidin-1-yl)propyl)amino)benzamide;
    • (460) 4-((3-(dimethylamino)propyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
    • (461) 4-((3-morpholinopropyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
    • (462) N-(3-oxo-7-(phenylamino)isoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide;
    • (463) 4-((3-(4-methylpiperazin-1-yl)propyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl) benzamide;
    • (464) 4-((3-hydroxypropyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
    • (465) N-(7-((3,5-bis(trifluoromethyl)phenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
    • (466) N-(7-((3,5-bis(trifluoromethyl)phenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide;
    • (467) N-(7-((3,5-bis(trifluoromethyl)phenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide;
    • (468) N-(7-((3,5-bis(trifluoromethyl)phenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide;
    • (469) N-(7-((2,3-dimethylphenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
    • (470) N-(7-((2,3-dimethylphenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide;
    • (471) N-(7-((2,3-dimethylphenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide;
    • (472) N-(7-((2,3-dimethylphenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide;
    • (473) N-(3-oxo-7-(o-tolylamino)isoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
    • (474) N-(7-((2-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
    • (475) N-(7-((2-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide;
    • (476) N-(3-oxo-7-(o-tolylamino)isoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide;
    • (477) N-(7-((2-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide;
    • (478) N-(7-((2-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide;
    • (479) N-(3-oxo-7-(phenylamino)isoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide;
    • (480) N-(3-oxo-7-(phenylamino)isoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide hydrochloride;
    • (481) 4-((2-aminoethyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
    • (482) N-(3-oxo-7-(o-tolylamino)isoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl) amino)benzamide;
    • (483) N-(3-oxo-7-(o-tolylamino)isoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl) amino)benzamide;
    • (484) 4-((4-hydroxybutyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
    • (485) 4-((2-acetamidoethyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
    • (486) 4-((3-aminopropyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
    • (487) 4-((2-hydroxyethyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
    • (488) 4-((2-hydroxy-3-(piperidin-1-yl)propyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
    • (489) (S)-4-((2-hydroxy-3-(piperidin-1-yl)propyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
    • (490) (R)-4-((2-hydroxy-3-(piperidin-1-yl)propyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
    • (491) 4-(4-aminopiperidin-1-yl)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide; and
    • (492) 4-((2-(azepan-1-yl)ethyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide.
  • The compound according to the present invention may exist as a pharmaceutically acceptable salt. Preferably, the pharmaceutically acceptable salt of the inventive compound is a salt formed with an inorganic or organic acid. Examples of the inorganic acid include hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, perchloric acid, bromic acid, and the like. Also, examples of the organic acid include acetic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, fumaric acid, maleic acid, malonic acid, phthalic acid, succinic acid, lactic acid, citric acid, gluconic acid, tartaric acid, salicylic acid, malic acid, oxalic acid, benzoic acid, embonic acid, aspartic acid, glutamic acid, and the like. Examples of organic bases which can be used for preparing an organic base addition salt include tris(hydroxymethyl)methylamine, dicyclohexylamine, and the like. Examples of amino acids which can be used for preparing an amino acid addition salt include natural amino acids such as alanine, glycine, and the like.
  • Said salts may be prepared by conventional methods known in the art, e.g., dissolving the compound of formula (I) in a water-miscible solvent such as methanol, ethanol, acetone, 1,4-dioxane, adding a free acid or free base thereto, and subjecting the mixture to crystallization.
  • Also, the compounds of the present invention may have asymmetric carbon centers and, thus, may exist as R- or S-isomer, racemic mixtures, individual enantiomers or mixtures thereof, and individual diastereomers or mixtures thereof. Such stereoisomers and mixtures thereof are all included within the scope of the present invention.
  • Additionally, solvates and hydrates of the compound of formula (I) are also included within the scope of the present invention. Such solvates and hydrate may be prepared by conventional methods known in the art. Preferably, the solvates and hydrates are non-toxic and water-soluble, and form 1 to 5 bonds with water or alcohol-based solvent (particularly, ethanol and the like).
  • Meanwhile, the present invention provides a pharmaceutical composition for the prevention or treatment of cancer, comprising a compound selected from the group consisting of the compound of formula (I), and a pharmaceutically acceptable salt, a hydrate and a solvate thereof.
  • Examples of said cancer include colorectal cancer, breast cancer, CNS cancer, colon cancer, non-small cell lung cancer, kidney cancer, prostate cancer, ovarian cancer, uterus cancer, stomach cancer, liver cancer, skin cancer, lung cancer, brain cancer, bladder cancer, esophageal cancer, pancreatic cancer, thyroid cancer, head and neck cancer, squamous cell carcinoma, osteosarcoma, B-cell or T-cell lymphoma, acute or chronic leukemia and multiple myeloma.
  • In addition, since the inventive compound of formula (I) can inhibit TNIK, IKKε and TBK1, it can also be used for the prevention or treatment of diseases associated with TNIK, IKKε and TB protein activation, e.g., chronic inflammation, and the like.
  • A pharmaceutical composition of the present invention may comprise one or more conventional non-toxic pharmaceutically acceptable additives as effective components, in addition to the compound of formula (I) or a pharmaceutically acceptable salt, a hydrate or a solvate thereof.
  • Examples of acceptable additives for the pharmaceutical composition of the present invention include sweeteners, binders, solubilizing agents, dissolution aids, wetting agents, emulsifiers, isotonic agents, adsorbents, disintegrants, antioxidants, preservatives, lubricants, fillers, fragrances, and the like, e.g., lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, glycine, silica, talc, stearic acid, stearin, magnesium stearate, magnesium aluminum silicate, starch, gelatin, tragacanth gum, alginic acid, sodium alginate, methylcellulose, sodium carboxymethyl cellulose, agar, water, ethanol, polyethylene glycol, polyvinyl pyrrolidone, sodium chloride, calcium chloride, orange essence, strawberry essence, vanilla flavor, etc.
  • A pharmaceutical composition of the present invention may be prepared as an oral dosage form such as a tablet, a pill, powders, a capsule, a syrup or an emulsion or a parenteral dosage form for intramuscular, intravenous or subcutaneous administration. Preferably, the pharmaceutical composition is prepared in an oral dosage form.
  • In the case where the pharmaceutical composition of the present invention is prepared as an oral dosage form, the inventive pharmaceutical composition may contain additives such as cellulose, calcium silicate, corn starch, lactose, sucrose, dextrose, calcium phosphate, stearic acid, magnesium stearate, calcium stearate, gelatin, talc, a surfactant, a suspension agent, an emulsifier, a diluent, etc.
  • Also, in the case where the pharmaceutical composition of the present invention is prepared as an injectable dosage form, the inventive pharmaceutical composition may contain additives such as water, brine, a glucose aqueous solution, an analog glucose aqueous solution, alcohol, glycol, ether, oil, a fatty acid, a fatty acid ester, a glyceride, a surfactant, a suspension agent, an emulsifier, etc.
  • Preferably, a proposed daily dose of the compound in accordance with the present invention for an adult patient (of approximately 70 kg body weight) may be in the range of 0.1 to 2,000 mg/day. The compound in accordance with the present invention may be administered in a single dose or in divided doses per day. It is understood that the daily dose should be determined in light of various relevant factors including health status, age, weight and sex of a subject to be treated, administration route and disease severity. Thus, the amount of proposed daily dose is not limited to the above-described range.
  • Hereinafter, the present invention is described in detail with reference to the following examples. However, these examples are merely presented to exemplify the present invention, and the scope of the present invention is not limited thereto.
  • The symbols and conventions used for describing the processes, schemes and examples of the present invention are consistent with those used in contemporary scientific literatures, for example, the Journal of the American Chemical Society or the Journal of Biological Chemistry. Unless otherwise noted, all starting materials were obtained from commercial suppliers and used without further purification.
  • The following are definitions of abbreviations that are used in the examples.
  • Hz (Hertz)
  • TLC (thin layer chromatography)
  • Tr (retention time)
  • RP (reverse phase)
  • MeOH (methanol)
  • i-PrOH (isopropanol)
  • TFA (trifluoroacetic acid)
  • TEA (triethylamine)
  • EtOH (ethanol)
  • THF (tetrahydrofuran)
  • DMSO (dimethylsulfoxide)
  • EtOAc (ethyl acetate)
  • DCM (dichloromethane)
  • HOAc (acetic acid)
  • DMF (N,N-dimethylformamide)
  • Ac (acetyl)
  • HOBt (1-hydroxybenzotriazole)
  • Bn (benzyl)
  • Boc (tert-butyloxycarbonyl)
  • mCPBA (meta-chloroperbenzoic acid)
  • FMOC (9-fluorenylmethoxycarbonyl)
  • DCC (dicyclohexylcarbodiimide)
  • Cbz (benzyloxycarbonyl)
  • NMM (N-methyl morpholine)
  • HOAt (1-hydroxy-7-azabenzotriazole)
  • TBAF (tetra-n-butylammonium fluoride)
  • THP (tetrahydro-2H-pyran-2-yl)
  • DMAP (4-dimethylaminopyridine)
  • HPLC (high pressure liquid chromatography)
  • BOP (bis(2-oxo-3-oxazolidinyl)phosphinic chloride);
  • EDCI (1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride)
  • HBTU (0-Benzotriazole-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate)
  • AIBN (2,2′-azobis(2-methylpropionitrile))
  • MeI (iodomethane)
  • DIPEA (diisopropylethylamine)
  • NaSMe (sodium thiomethoxide)
  • DAST (diethylaminosulfur trifluoride)
  • DMAc (dimethylacetamide)
  • NBS (N-bromosuccinimide)
  • BPO (benzoyl peroxide)
  • MTBE (tert-butyl methyl ether)
  • DME (dimethoxyethane)
  • LiHMDS (lithium bis(trimethylsilyl)amide
  • TMS (trimethylsilyl)
  • S-Phos (2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl)
  • RBF (round-bottom flask)
  • mCPBA (3-chloroperbenzoic acid)
  • Pd2dba3 (tris(dibenzylideneacetone)dipalladium(0))
  • Xphos (2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl)
  • BrettPhos (2-(dicyclohexylphosphino)3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl)
  • While the present invention has been described with respect to specific embodiments, it should be recognized that various modifications and changes may be made to the invention by those skilled in the art which also fall within the scope of the invention as defined by the appended claims.
  • All references to ether are to diethyl ether; brine refers to a saturated aqueous solution of NaCl. Unless otherwise indicated, all temperatures are expressed in ° C. (degrees Centigrade). All reactions were conducted under an inert atmosphere at room temperature unless otherwise noted, and all solvents are of the highest available purity unless otherwise indicated.
  • Microwave reaction was conducted with a Biotage Initiator™ microwave synthesizer.
  • 1H NMR spectra were recorded on Bruker Ultrashield 400 plus spectrometer. Chemical shifts were expressed in parts per million (ppm, δ units). Coupling constants are in units of hertz (Hz). Splitting patterns describe apparent multiplicities and are designated as s (singlet), d (doublet), t (triplet), q (quartet), quint (quintet), m (multiplet) or br (broad).
  • Mass spectra were obtained with either Quattro LC Triple Quadruple Tandem Mass Spectrometer (ESI; Micromass) or 1200LC/MSD (ESI; Agilent).
  • For preparative HPLC, ca 100 mg of a product was injected into 1 mL of DMSO onto a SunFire™ Prep C18 OBD 5 μm 19×100 mm Column with a 10 min gradient from 10% CH3CN to 90% CH3CN in H2O (purification systems from Gilson, Inc). Flash chromatography was carried out using Merck silica gel 60 (230-400 mesh). Biotage SP1™ FLASH Purification System and Biotage Isolera™ FLASH Purification System were used for normal phase column chromatography with ethyl acetate and hexane. Most of the reactions were monitored by thin-layer chromatography on 0.25 mm E. Merck silica gel plates (60F-254), visualized with UV light using a 5% ethanolic phosphomolybdic acid or p-anisaldehyde solution.
  • The following synthetic schemes are merely illustrative of the methods by which the compounds of the invention may be prepared and are not intended to limit the scope of the invention as defined in the appended claims.
    • Preparation Example 1 Preparation of 1H-isoindolinone
  • Figure US20160311772A1-20161027-C00003
    Figure US20160311772A1-20161027-C00004
    • Step 1: Preparation of methyl 3-bromo-2-methylbenzoate (2)
  • To a solution of 3-bromo-2-methylbenzoic acid 1 (10.8 g, 0.05 mol) in MeOH (92 mL) was added conc. H2SO4 (17.6 mL, 0.32 mol) dropwise at room temperature. The resulting mixture was then stirred at 60° C. for 1.5 hours, then poured into saturated NaHCO3 (500 mL) slowly, extracted with EtOAc (3×300 mL), dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give the title product 2 (10.9 g) as a pale brown oil.
  • 1H NMR (400 MHz, CDCl3) δ 7.71-7.68 (m, 2H), 7.11-7.07 (t, J=7.1 Hz, 1H), 3.90 (s, 3H), 2.63 (s, 3H). [M+H]+: 229.
    • Step 2: Preparation of methyl 3-bromo-2-(bromomethyl)benzoate (3)
  • To a solution of methyl 3-bromo-2-methylbenzoate 2 (10.9 g, 47.6 mmol) in CCl4 (138 mL) at refluxing was added the mixture of NBS (9.74 g, 54.7 mmol) and BPO (0.58 g, 2.38 mmol) as three portions. Then, the resulting mixture was stirred at refluxing for 3.5 hours, then cooled to room temperature, and filtered. The filtrate was concentrated to give the crude product 3 (15.0 g) as an oil, which was directly used in the next step without further purification.
  • 1H NMR (400 MHz, CDCl3) δ 7.89-7.87 (d, J=7.6 Hz, 1H), 7.77-7.75 (d, J=8.0 Hz, 1H), 7.26-7.21 (t, J=8.0 Hz, 1H), 5.13 (s, 2H), 3.95 (s, 3H).
    • Step 3: Preparation of 4-bromoisoindolin-1-one (4)
  • To a solution of methyl 3-bromo-2-(bromomethyl)benzoate 3 (8.3 g, 26.9 mmol) in THF (100 mL) was added concentrated NH4OH (9 mL) dropwise. After stirring them at room temperature overnight, the mixture was concentrated in vacuo to give the residue, which was then washed with water and MTBE, and dried to give the title product 4 (4.14 g).
  • 1H NMR (400 Hz, CDCl3) δ 7.85-7.83 (d, J=7.5 Hz, 1H), 7.72-7.70 (d, J=7.9 Hz, 1H), 7.42-7.38 (t, J=7.7 Hz, 1H), 6.81 (s, 1H), 4.39 (s, 2H).
    • Step 4: Preparation of 4-bromo-7-nitroisoindolin-1-one (5)
  • To a solution of 4-bromoisoindolin-1-one 4 (3.0 g, 14.1 mmol) in conc. H2SO4 (6 mL) at 0° C. was added dropwise a solution of conc. HNO3 (1 mL) in conc. H2SO4 (6 mL) The resulting mixture was then stirred at room temperature overnight, then poured over ice, and filtered. The filter cake was washed with water, MTBE, dried in vacuo to give the title product 5 (3.0 g).
  • 1H NMR (400 MHz, DMSO-d6) δ 9.17 (s, 1H), 8.06-8.04 (d, J=8.4 Hz, 1H), 7.89-7.87 (d, J=8.4 Hz, 1H), 4.39 (s, 2H).
    • Step 5: Preparation of 7-amino-4-bromoisoindolin-1-one (6)
  • To a suspension solution of Fe (54.6 g, 0.975 mol) in H2O (500 mL) and EtOH (750 mL) was added HCl (5 mL), and the mixture was stirred for 0.5 hour at 50° C., then 4-bromo-7-nitroisoindolin-1-one 5 (50.0 g, 0.195 mol) was added as portions at refluxing. After stirred at refluxing for 1 hour, the reaction mixture was filtered through a Celite pad when it was hot, and the filter cake was washed with THF (2 L). And then the filtrate was concentrated in vacuo to give the title product 6 (40 g).
  • 1H NMR (400 MHz, DMSO-d6) δ 8.35 (s, 1H), 7.33-7.31 (d, J=8.6 Hz, 1H), 6.56-6.54 (d, J=8.6 Hz, 1H), 6.18 (s, 2H), 4.13 (s, 2H). [M+H]+: 227.
    • Step 6: Preparation of N-(7-bromo-3-oxoisoindolin-4-yl)benzamide (8)
  • To a suspension solution of 7-amino-4-bromoisoindolin-1-one 6 (40.0 g, 0.176 mol) in THF (1.9 L) was added NMM (54.3 g, 0.528 mol) at 0° C., then benzoyl chloride 7 (49.5 g, 0.352 mol) was added dropwise over 20 min. The resulting reaction mixture was then stirred at room temperature overnight, poured into water (400 mL), concentrated in vacuo to remove THF. Then the residue was washed with EtOAc (3×300 mL), and filtered to give the title product 8 (56 g).
  • 1H NMR (400 Hz, DMSO-d6) δ 11.41 (s, 1H), 9.17 (s, 1H), 8.43-8.41 (d, J=8.6 Hz, 1H), 7.96-7.94 (d, J=7.4 Hz, 2H), 7.80-7.78 (d, J=8.6 Hz, 1H), 7.67-7.59 (m, 3H), 4.36 (s, 2H). [M+H]+: 331.
    • Example 1 N-(7-(2-ethylphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00005
  • To a suspension solution of the intermediate 8 (200 mg, 0.604 mmol), (2-ethylphenyl)boronic acid (181 mg, 1.208 mmol), Na2CO3 (256 mg, 2.416 mmol) in DME (7 mL) and H2O (1.7 mL) was added Pd(PPh3)4 (69 mg, 0.060 mmol), then the mixture was purged with nitrogen, and stirred at 100° C. for 5 hours. The reaction mixture was then cooled to room temperature, diluted with EtOAc (50 mL) and water (50 mL), and filtered. The filtrate was washed with brine, and the organic phase was concentrated in vacuo and purified by chromatography to give the title compound 10 (77 mg).
  • 1H NMR (400 MHz, DMSO-d6) δ 11.60 (s, 1H), 8.97 (s, 1H), 8.54-8.52 (d, J=8.32 Hz, 1H), 8.00-7.98 (m, 2H), 7.70-7.61 (m, 3H), 7.48-7.45 (d, J=8.24 Hz, 1H), 7.40-7.34 (m, 2H), 7.29-7.24 (m, 2H), 4.17 (s, 2H) 2.47-2.43 (m, 2H), 1.01-0.97 (m, 3H). [M+H]+ 357.
  • The following compounds of Examples 2 to 41 were obtained by using corresponding starting materials and repeating the procedure of Example 1.
    • Example 2 N-(7-(3-isopropylphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00006
  • 1H NMR (400 MHz, DMSO-d6) δ 11.74 (s, 1H), 9.06 (s, 1H), 8.59-8.57 (d, J=8.40 Hz, 1H), 8.00-7.98 (m, 2H), 7.73-7.61 (m, 4H), 7.48 (s, 1H), 7.42-7.40 (m, 2H), 7.29-7.27 (d, J=6.24 Hz, 1H), 4.61 (s, 2H), 3.02-2.95 (m, 1H) 1.27-1.26 (m, 6H). [M+H]+: 371.
    • Example 3 N-(7-(4-(tert-butyl)phenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00007
  • 1H NMR (400 MHz, DMSO-d6) δ 11.74 (s, 1H), 9.08 (s, 1H), 8.58-8.56 (d, J=8.44 Hz, 1H), 8.00-7.98 (m, 2H), 7.72-7.61 (m, 4H), 7.57-7.55 (m, 2H), 7.52-7.50 (m, 2H), 4.62 (s, 2H), 1.33-1.29 (s, 9H). [M+H]+: 385.
    • Example 4 N-(3-oxo-7-(2-(trifluoromethoxy)phenyl)isoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00008
  • 1H NMR (400 MHz, DMSO-d6) δ 11.65 (s, 1H), 9.04 (s, 1H), 8.58-8.56 (d, J=8.44 Hz, 1H), 8.00-7.98 (m, 2H), 7.70-7.51 (m, 8H), 4.31 (s, 2H). [M+H]+: 413.
    • Example 5 N-(3-oxo-7-(3-(trifluoromethoxy)phenyl)isoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00009
  • 1H NMR (400 MHz, DMSO-d6) δ 11.76 (s, 1H), 9.11 (s, 1H), 8.61-8.59 (d, J=8.40 Hz, 1H), 8.00-7.99 (m, 2H), 7.79-7.77 (d, J=8.44 Hz, 1H), 7.70-7.61 (m, 6H), 7.42-7.40 (d, J=8.20 Hz, 1H), 4.64 (s, 2H). [M+H]+: 413.
    • Example 6 N-(7-(2-isopropoxyphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00010
  • 1H NMR (400 MHz, DMSO-d6) δ 11.66 (s, 1H), 8.93 (s, 1H), 8.53-8.51 (d, J=8.36 Hz, 1H), 8.00-7.98 (m, 2H), 7.68-7.61 (m, 3H), 7.56-7.54 (d, J=8.36 Hz, 1H), 7.39-7.33 (m, 2H), 7.16-7.14 (d, J=8.20 Hz, 1H), 7.05-7.01 (m, 1H), 4.58-4.52 (m, 1H), 4.34 (s, 2H), 1.16-1.15 (m, 6H). [M+H]+: 387.
    • Example 7 N-(7-(3-isopropoxyphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00011
  • 1H NMR (400 MHz, DMSO-d6) δ 11.74 (s, 1H), 9.07 (s, 1H), 8.58-8.56 (d, J=8.44 Hz, 1H), 8.00-7.89 (m, 2H), 7.73-7.61 (m, 4H), 7.40-7.36 (m, 1H), 7.15-7.11 (m, 2H), 6.96-6.93 (d, J=8.20 Hz, 1H), 4.75-4.69 (m, 1H), 4.61 (s, 2H), 1.31-1.29 (m, 6H). [M+H]+: 397.
    • Example 8 Methyl 2-(7-benzamido-1-oxoisoindolin-4-yl)benzoate
  • Figure US20160311772A1-20161027-C00012
  • 1H NMR (400 MHz, DMSO-d6) δ 11.61 (s, 1H), 8.96 (s, 1H), 8.51-8.49 (d, J=8.28 Hz, 1H), 8.00-7.98 (m, 2H), 7.92-7.90 (d, J=7.88 Hz, 1H), 7.70-7.61 (m, 4H), 7.58-7.56 (m, 1H), 7.51-7.49 (d, J=7.48 Hz, 1H), 7.38-7.36 (d, J=8.28 Hz, 1H), 4.20 (s, 2H), 3.60 (s, 3H). [M+H]+: 387.
    • Example 9 Methyl 3-(7-benzamido-1-oxoisoindolin-4-yl)benzoate
  • Figure US20160311772A1-20161027-C00013
  • 1H NMR (400 MHz, DMSO-d6) δ 11.75 (s, 1H), 9.11 (s, 1H), 8.62-8.60 (d, J=8.44 Hz, 1H), 8.12 (s, 1H), 8.01-7.99 (m, 3H), 7.95-7.93 (d, J=7.64 Hz, 1H), 7.79-7.77 (d, J=8.44 Hz, 1H), 7.70-7.62 (m, 4H), 4.61 (s, 2H), 3.90 (s, 3H). [M+H]+: 387.
    • Example 10 Methyl 4-(7-benzamido-1-oxoisoindolin-4-yl)benzoate
  • Figure US20160311772A1-20161027-C00014
  • 1H NMR (400 MHz, DMSO-d6) δ 11.77 (s, 1H), 9.13 (s, 1H), 8.62-8.60 (d, J=8.5 Hz, 1H), 8.07-8.05 (d, J=8.4 Hz, 2H), 7.99-7.98 (d, J=7.0 Hz, 2H), 7.82-7.78 (m, 3H), 7.70-7.61 (m, 3H), 4.64 (s, 2H), 3.89 (s, 3H). [M+H]+: 387.
    • Example 11 N-(7-(2-acetylphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00015
  • 1H NMR (400 MHz, DMSO-d6) δ 11.62 (s, 1H), 9.00 (s, 1H), 8.51-8.49 (d, J=8.28 Hz, 1H), 8.01-7.99 (m, 2H), 7.80-7.78 (d, J=7.56 Hz, 1H), 7.69-7.61 (m, 4H), 7.58-7.50 (m, 2H), 7.37-7.35 (d, J=8.32 Hz, 1H), 4.27 (s, 2H), 2.33 (s, 3H). [M+H]+: 371.
    • Example 12 N-(7-(3-acetylphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00016
  • 1H NMR (400 MHz, DMSO-d6) δ 11.76 (s, 1H), 9.12 (s, 1H), 8.62-8.60 (d, J=8.40 Hz, 1H), 8.13 (s, 1H), 8.01-7.97 (m, 3H), 7.92-7.90 (d, J=7.76 Hz, 1H), 7.81-7.79 (d, J=8.44 Hz, 1H), 7.71-7.62 (m, 4H), 4.63 (s, 2H), 2.66 (s, 3H). [M+H]+: 371.
    • Example 13 N-(7-(4-acetylphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00017
  • 1H NMR (400 MHz, DMSO-d6) δ 11.78 (s, 1H), 9.13 (s, 1H), 8.62-8.60 (d, J=8.44 Hz, 1H), 8.07-8.05 (m, 2H), 8.01-7.99 (m, 2H), 7.82-7.78 (m, 3H), 7.69-7.61 (m, 3H), 4.65 (s, 2H), 2.63 (s, 3H). [M+H]+: 371.
    • Example 14 N-(7-(2-(methylthio)phenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00018
  • 1H NMR (400 MHz, DMSO-d6) δ 11.60 (s, 1H), 8.95 (s, 1H), 8.53-8.51 (d, J=8.28 Hz, 1H), 8.00-7.98 (m, 2H), 7.68-7.61 (m, 3H), 7.50-7.37 (m, 3H), 7.29-7.25 (m, 2H), 4.24 (s, 2H), 2.38 (s, 3H). [M+H]+: 375.
    • Example 15 N-(7-(2,4-difluorophenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00019
  • 1H NMR (400 MHz, DMSO-d6) δ 11.69 (s, 1H), 9.05 (s, 1H), 8.58-8.56 (d, J=8.40 Hz, 1H), 8.00-7.98 (m, 2H), 7.68-7.61 (m, 5H), 7.45-7.39 (m, 1H), 7.24-7.20 (t, J=8.36 Hz, 1H), 4.39 (s, 2H). [M+H]+: 365.
    • Example 16 N-(7-(2,3-dimethylphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00020
  • 1H NMR (400 MHz, DMSO-d6) δ 11.61 (s, 1H), 8.96 (s, 1H), 8.54-8.52 (d, J=8.24 Hz, 1H), 8.00-7.98 (m, 2H), 7.70-7.61 (m, 3H), 7.43-7.41 (d, J=8.28 Hz, 1H), 7.23-7.21 (d, J=7.44 Hz, 1H), 7.18-7.14 (m, 1H), 7.11-7.09 (d, J=7.36 Hz, 1H), 4.17-4.16 (s, 2H), 2.31 (s, 3H), 2.03 (s, 3H). [M+H]+: 357.
    • Example 17 N-(7-(2,3-dichlorophenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00021
  • 1H NMR (400 MHz, DMSO-d6) δ 11.63 (s, 1H), 9.03 (s, 1H), 8.57-8.55 (d, J=8.40 Hz, 1H), 8.00-7.98 (m, 2H), 7.74-7.61 (m, 4H), 7.58-7.56 (d, J=8.36 Hz, 1H), 7.51-7.45 (m, 2H), 4.28 (s, 2H). [M+H]+: 397.
    • Example 18 N-(7-(2,4-dichlorophenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00022
  • 1H NMR (400 MHz, DMSO-d6) δ 11.63 (s, 1H), 9.02 (s, 1H), 8.57-8.55 (d, J=8.40 Hz, 1H), 8.00-7.98 (m, 2H), 7.80 (s, 1H), 7.70-7.61 (m, 3H), 7.56-7.52 (m, 3H), 4.29 (s, 2H). [M+H]+: 397.
    • Example 19 N-(7-(2,5-dichlorophenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00023
  • 1H NMR (400 MHz, DMSO-d6) δ 11.64 (s, 1H), 9.04 (s, 1H), 8.57-8.55 (d, J=8.36 Hz, 1H), 8.00-7.99 (m, 2H), 7.69-7.61 (m, 5H), 7.58-7.53 (m, 2H), 4.32 (s, 2H). [M+H]+: 397.
    • Example 20 N-(7-(3,4-dichlorophenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00024
  • 1H NMR (400 MHz, DMSO-d6) δ 11.74 (s, 1H), 9.11 (s, 1H), 8.59-8.57 (d, J=8.48 Hz, 1H), 8.00-7.98 (m, 2H), 7.90 (s, 1H), 7.77-7.72 (m, 2H), 7.68-7.66 (m, 1H), 7.64-7.61 (m, 3H), 4.63 (s, 2H). [M+H]+: 397.
    • Example 21 N-(7-(3,5-dichlorophenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00025
  • 1H NMR (400 MHz, DMSO-d6) δ 11.75 (s, 1H), 9.11 (s, 1H), 8.59-8.57 (d, J=8.48 Hz, 1H), 8.00-7.98 (m, 2H), 7.79-7.77 (d, J=8.48 Hz, 1H), 7.69-7.61 (m, 6H), 4.64 (s, 2H). [M+H]+: 397.
    • Example 22 N-(7-(4-fluoro-2-methoxyphenyl)-3-oxoisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00026
  • 1H NMR (400 MHz, DMSO-d6) δ 11.65 (s, 1H), 8.96 (s, 1H), 8.52-8.50 (d, J=8.44 Hz, 1H), 8.00-7.98 (m, 2H), 7.68-7.63 (m, 3H), 7.52-7.50 (d, J=8.36 Hz, 1H), 7.37-7.34 (m, 1H), 7.08-7.04 (dd, J=11.44 Hz, 1H), 6.88-6.87 (t, J=6.52 Hz, 1H), 4.26 (s, 2H), 3.79 (s, 3H). [M+H]+: 377.
    • Example 23 N-(7-(2-chloro-3-fluorophenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00027
  • 1H NMR (400 MHz, DMSO-d6) δ 11.70 (s, 1H), 9.06 (s, 1H), 8.59-8.57 (d, J=8.28 Hz, 1H), 8.01-7.99 (m, 2H), 7.68-7.61 (m, 5H), 7.57-7.56 (m, 1H), 7.37-7.35 (m, 1H), 4.41 (s, 2H). [M+H]+: 381.
    • Example 24 N-(7-(2-fluoro-3-methoxyphenyl)-3-oxoisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00028
  • 1H NMR (400 MHz, DMSO-d6) δ 11.68 (s, 1H), 9.01 (s, 1H), 8.58-8.56 (d, J=8.36 Hz, 1H), 8.00-7.98 (m, 2H), 7.70-7.61 (m, 4H), 7.25-7.21 (m, 2H), 7.10-7.07 (m, 1H), 4.37 (s, 2H), 3.90 (s, 3H). [M+H]+: 377.
    • Example 25 N-(3-oxo-7-(2,3,4-trimethoxyphenyl)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00029
  • 1H NMR (400 MHz, DMSO-d6) δ 11.65 (s, 1H), 8.95 (s, 1H), 8.53-8.51 (d, J=8.44 Hz, 1H), 8.00-7.98 (m, 2H), 7.68-7.61 (m, 3H), 7.55-7.52 (d, J=8.40 Hz, 1H), 7.09-7.07 (d, J=8.56 Hz, 1H), 6.91-6.89 (d, J=8.72 Hz, 1H), 4.33 (s, 2H), 3.85 (s, 3H), 3.51 (s, 3H), 3.81 (s, 3H). [M+H]+: 419.
    • Example 26 N-(7-(3,4-dimethylphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00030
  • 1HNMR (400 MHz, DMSO-d6) δ 11.74 (s, 1H), 9.08 (s, 1H), 8.57 (d, J=8.6 Hz, 1H), 8.00 (d, J=8.6 Hz, 2H), 7.72-7.59 (m, 4H), 7.40 (s, 1H), 7.34 (d, J=7.8 Hz, 1H), 7.25 (d, J=7.8 Hz, 1H), 4.60 (s, 2H), 2.30 (d, J=10.9 Hz, 1H); MS (ESI) m/z 357 (M+H)+.
    • Example 27 N-(7-(3,5-dimethylphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00031
  • 1H NMR (400 MHz, DMSO-d6) δ 11.75 (s, 1H), 9.08 (s, 1H), 8.57 (d, J=8.6 Hz, 1H), 8.00 (d, J=8.4 Hz, 2H), 7.71-7.58 (m, 4H), 7.23 (s, 2H), 7.05 (s, 1H), 4.60 (s, 2H), 2.36 (s, 6H); MS (ESI) m/z 357 (M+H)+.
    • Example 28 N-(7-(2,6-dimethylphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00032
  • 1H NMR (400 MHz, DMSO-d6) δ 11.58 (s, 1H), 8.96 (s, 1H), 8.57 (d, J=8.3 Hz, 1H), 8.01 (d, J=7.3 Hz, 2H), 7.72-7.59 (m, 3H), 7.35 (d, J=8.2 Hz, 1H), 7.23-7.14 (m, 3H), 4.03 (s, 2H), 1.97 (s, 6H); MS (ESI) m/z 357 (M+H)+.
    • Example 29 N-(7-ethyl-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00033
  • 1H NMR (400 MHz, DMSO-d6) δ 11.49 (s, 1H), 8.95 (s, 1H), 8.42 (d, J=8.3 Hz, 1H), 7.97 (d, J=7.0 Hz, 2H), 7.72-7.58 (m, 4H), 7.46 (d, J=8.3 Hz, 1H), 4.45 (s, 2H), 2.64 (q, J=7.6 Hz, 2H), 1.23 (t, J=7.6 Hz, 3H); MS (ESI) m/z 281 (M+H)+.
    • Example 30 N-(7-(3,5-difluorophenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00034
  • 1H NMR (400 MHz, DMSO-d6) δ 11.79 (s, 1H), 9.16 (s, 1H), 8.60 (d, J=8.4 Hz, 1H), 8.00 (d, J=7.2 Hz, 2H), 7.81 (d, J=8.5 Hz, 1H), 7.70-7.61 (m, 3H), 7.41 (d, J=7.0 Hz, 1H), 7.30 (t, J=9.3 Hz, 1H), 4.68 (s, 2H); MS (ESI) m/z 365 (M+H)+.
    • Example 31 N-(7-(2,5-dimethylphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00035
  • 1H NMR (400 MHz, DMSO-d6) δ 11.63 (s, 1H), 8.99 (s, 1H), 8.54 (d, J=8.3 Hz, 1H), 8.01 (d, J=7.2 Hz, 2H), 7.70-7.61 (m, 3H), 7.46 (d, J=8.3 Hz, 1H), 7.24 (d, J=7.7 Hz, 1H), 7.15-7.10 (m, 2H), 4.22 (s, 2H), 2.32 (s, 3H), 2.10 (s, 3H); MS (ESI) m/z 357 (M+H)+.
    • Example 32 N-(7-(2,5-difluorophenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00036
  • 1H NMR (400 MHz, DMSO-d6) δ 11.72 (s, 1H), 9.08 (s, 1H), 8.60 (d, J=8.4 Hz, 1H), 8.01 (d, J=7.1 Hz, 2H), 7.73-7.61 (m, 4H), 7.55-7.31 (m, 3H), 4.46 (s, 2H); MS (ESI) m/z 365 (M+H)+.
    • Example 33 N-(7-(3,4-difluorophenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00037
  • 1H NMR (400 MHz, DMSO-d6) δ 11.76 (s, 1H), 9.13 (s, 1H), 8.59 (d, J=8.5 Hz, 1H), 8.01 (d, J=7.1 Hz, 2H), 7.81-7.49 (m, 7H), 4.64 (s, 2H); MS (ESI) m/z 365 (M+H)+.
    • Example 34 N-(7-(2,3-difluorophenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00038
  • 1H NMR (400 MHz, DMSO-d6) δ 11.72 (s, 1H), 9.09 (s, 1H), 8.61 (d, J=8.4 Hz, 1H), 8.01 (d, J=7.3 Hz, 2H), 7.73-7.61 (m, 4H), 7.57-7.31 (m, 3H), 4.44 (s, 2H); MS (ESI) m/z 365 (M+H)+.
    • Example 35 N-(7-butyl-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00039
  • 1H NMR (400 MHz, DMSO-d6) δ 11.49 (s, 1H), 8.94 (s, 1H), 8.40 (d, J=8.2 Hz, 1H), 7.97 (d, J=7.2 Hz, 2H), 7.71-7.59 (m, 3H), 7.42 (d, J=8.3 Hz, 1H), 4.43 (s, 2H), 2.61 (t, J=7.6 Hz, 2H), 1.65-1.1.53 (m, 2H), 1.39-1.29 (m, 2H), 0.93 (t, J=7.3 Hz, 2H); MS (ESI) m/z 309 (M+H)+.
    • Example 36 4-Fluoro-N-(3-oxo-7-propylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00040
  • MS (ESI) m/z 313 (M+H)+.
    • Example 37 N-(7-methyl-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00041
  • 1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 8.93 (s, 1H), 8.36 (d, J=8.2 Hz, 1H), 7.95 (d, J=7.2 Hz, 2H), 7.71-7.57 (m, 3H), 7.40 (d, J=8.2 Hz, 1H), 4.38 (s, 2H), 2.28 (s, 3H); MS (ESI) m/z 267 (M+H)+.
    • Example 38 N-(7-(2,4-dimethylphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00042
  • 1H NMR (400 MHz, DMSO-d6) δ 11.63 (s, 1H), 8.95 (s, 1H), 8.53 (d, J=8.3 Hz, 1H), 8.00 (d, J=7.2 Hz, 2H), 7.70-7.61 (m, 3H), 7.46 (d, J=8.3 Hz, 1H), 7.19-7.07 (m, 32H), 4.20 (s, 2H), 2.34 (s, 3H), 2.11 (s, 3H); MS (ESI) m/z 357 (M+H)+.
    • Example 39 N-(7-(4-ethylphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00043
  • 1H NMR (400 MHz, DMSO-d6) δ 11.75 (s, 1H), 9.09 (s, 1H), 8.58 (d, J=8.4 Hz, 1H), 8.00 (d, J=7.0 Hz, 2H), 7.74-7.59 (m, 4H), 7.55 (d, J=8.1 Hz, 2H), 7.34 (d, J=8.0 Hz, 2H), 4.62 (s, 2H), 2.68 (q, J=7.6 Hz, 2H), 1.25 (t, J=7.6 Hz, 3H); MS (ESI) m/z 357 (M+H)+.
    • Example 40 N-(7-(4-isopropoxyphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00044
  • 1H NMR (400 MHz, DMSO-d6) δ 11.74 (s, 1H), 9.08 (s, 1H), 8.57 (d, J=8.4 Hz, 1H), 8.00 (d, J=7.1 Hz, 2H), 7.70-7.61 (m, 4H), 7.55 (d, J=8.6 Hz, 2H), 7.02 (d, J=8.6 Hz, 2H), 4.71-4.65 (m, 1H), 4.60 (s, 2H), 1.32 (d, J=6.0 Hz, 6H); MS (ESI) m/z 387 (M+H)+.
    • Example 41 N-(7-(4-(methylthio)phenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00045
  • 1H NMR (400 MHz, DMSO-d6) δ 11.76 (s, 1H), 9.10 (s, 1H), 8.59 (d, J=8.4 Hz, 1H), 8.01 (d, J=7.1 Hz, 2H), 7.75-7.55 (m, 6H), 7.38 (d, J=8.3 Hz, 2H), 4.62 (s, 2H), 2.52 (s, 3H); MS (ESI) m/z 375 (M+H)+.
    • Example 42 N-(7-(3-ethylphenyl)-3-oxoisoindolin-4-yl)benzamide Step 1: Preparation of N-(3-oxo-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00046
  • A suspension solution of N-(7-bromo-3-oxoisoindolin-4-yl)benzamide (3.0 g, 9.06 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (6.9 g, 27.18 mmol), KOAc (3.1 g, 31.71 mmol), and PdCl2(dppf) (0.33 g, 0.45 mmol) in 1,4-dioxane (120 mL) was purged with nitrogen, and then stirred at 95° C. overnight. The reaction mixture was then cooled to room temperature, concentrated in vacuo, and washed with water to give the crude product, which was purified by column chromatography to give the intermediate 12 (1.9 g).
  • 1H NMR (400 MHz, DMSO-d6) δ 11.70 (s, 1H), 8.97 (s, 1H), 8.48-8.46 (d, J=8.1 Hz, 1H), 7.98-7.97 (d, J=7.2 Hz, 2H), 7.89-7.87 (d, J=8.2 Hz, 1H), 7.70-7.61 (m, 3H), 4.46 (s, 2H), 1.32 (s, 12H).
    • Step 2: Preparation of N-(7-(3-ethylphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00047
  • To a suspension solution of 1-bromo-3-ethylbenzene (400 mg, 2.161 mol), the intermediate 12 (1.062 g, 2.809 mol) and Na2CO3 (458 mg, 4.322 mol) in DME (12 mL) and H2O (3 mL) was added Pd(PPh3)4 (250 mg, 0.216 mol), and the mixture was purged with nitrogen, and stirred at 100° C. for 5 hours. The reaction mixture was then cooled to room temperature, diluted with EtOAc (100 mL) and water (100 mL), filtered; the filtrate was washed with brine (200 mL); and the organic phase was concentrated in vacuo and purified by column chromatography to give the title product 14.
  • 1H NMR (400 MHz, DMSO-d6) δ 11.74 (s, 1H), 9.06 (s, 1H), 8.59-8.58 (d, J=8.4 Hz, 1H), 8.00-7.98 (d, J=7.0 Hz, 2H), 7.22-7.61 (m, 4H), 7.45-7.38 (m, 3H), 7.26-7.24 (d, J=7.0 Hz, 1H), 4.61 (s, 2H), 2.72-2.66 (q, J=7.5 Hz, 2H), 1.26-1.22 (t, J=7.6 Hz, 3H).
  • The following compounds of Examples 43 to 59 were obtained by using corresponding starting materials and repeating the procedure of Example 42.
    • Example 43 N-(3-oxo-7-(2-propoxyphenyl)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00048
  • 1H NMR (400 MHz, DMSO-d6) δ 11.66 (s, 1H), 8.96 (s, 1H), 8.53-8.51 (d, J=8.36 Hz, 1H), 8.00-7.98 (m, 2H), 7.68-7.61 (m, 3H), 7.56-7.54 (d, J=8.36 Hz, 1H), 7.40-7.33 (m, 2H), 7.15-7.13 (d, J=8.20 Hz, 1H), 7.06-7.02 (m, 1H), 4.32 (s, 2H), 3.96-3.93 (m, 2H), 1.60-1.59 (m, 2H), 0.84-0.81 (m, 3H). [M+Na]+409.3
    • Example 44 N-(3-oxo-7-(3-propoxyphenyl)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00049
  • 1H NMR (400 MHz, DMSO-d6) δ 11.74 (s, 1H), 9.07 (s, 1H), 8.58-8.56 (d, J=8.4 Hz, 1H), 8.00-7.98 (d, J=7.0 Hz, 2H), 7.74-7.71 (d, J=8.4 Hz, 1H), 7.68-7.61 (m, 3H), 7.40-7.36 (t, J=15.8 Hz, 1H), 7.17-7.13 (m, 2H), 6.97-6.95 (dd, J=6.1 Hz, J=10.3 Hz, 1H), 4.60 (s, 2H), 4.02-2.99 (t, J=6.5 Hz, 2H), 1.78-1.73 (m, 2H), 1.02-0.98 (t, J=7.4 Hz, 3H). [M+Na]+409.2.
    • Example 45 N-(7-(2-butoxyphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00050
  • 1H NMR (400 MHz, DMSO-d6) δ 11.65 (s, 1H), 8.94 (s, 1H), 8.52-8.50 (d, J=8.36 Hz, 1H), 8.00-7.98 (m, 2H), 7.70-7.61 (m, 3H), 7.55-7.53 (d, J=8.36 Hz, 1H), 7.40-7.32 (m, 2H), 7.15-7.13 (d, J=8.16 Hz, 1H), 7.06-7.02 (m, 1H), 4.31 (s, 2H), 3.97-3.98 (m, 2H), 1.60-1.53 (m, 2H), 1.27-1.24 (m, 2H), 0.84-0.80 (m, 3H). [M+H]+: 401.4.
    • Example 46 N-(7-(3-butoxyphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00051
  • 1H NMR (400 MHz, DMSO-d6) δ 11.74 (s, 1H), 9.07 (s, 1H), 8.58-8.56 (d, J=8.44 Hz, 1H), 8.00-7.98 (m, 2H), 7.74-7.72 (d, J=8.44 Hz, 1H), 7.68-7.61 (m, 3H), 7.40-7.36 (m, 1H), 7.17-7.13 (m, 2H), 6.97-6.95 (d, J=8.16 Hz, 1H), 4.60 (s, 2H), 4.04-4.03 (m, 2H), 1.71-1.72 (m, 2H), 1.47-1.45 (m, 2H), 0.97-0.93 (m, 3H). [M+H]+: 401.2.
    • Example 47 N-(7-(2-(methylsulfonyl)phenyl)-3-oxoisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00052
  • 1H NMR (400 MHz, DMSO-d6) δ 11.60 (s, 1H), 8.96 (s, 1H), 8.54-8.52 (d, J=8.3 Hz, 1H), 8.15-8.13 (d, J=7.6 Hz, 1H), 8.00-7.99 (d, J=7.2 Hz, 2H), 7.81-7.79 (t, J=6.6 Hz, 1H), 7.76-7.58 (m, 5H), 7.54-7.52 (d, J=7.2 Hz, 1H), 7.19-4.15 (d, J=16.4 Hz, 1H), 2.90 (s, 3H). [M+H]+: 407.3.
    • Example 48 N-(7-(3-fluoro-2-methoxyphenyl)-3-oxoisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00053
  • 1H NMR (400 MHz, DMSO-d6) δ 11.67 (s, 1H), 9.00 (s, 1H), 8.57-8.55 (d, J=8.4 Hz, 1H), 8.00-7.98 (d, J=6.9 Hz, 2H), 7.70-7.59 (m, 4H), 7.37-7.32 (m, 1H), 7.25-7.18 (m, 2H), 4.34 (s, 2H), 3.62 (s, 3H). [M+Na]+: 399.3
    • Example 49 N-(7-(4-chloro-2-methoxyphenyl)-3-oxoisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00054
  • 1H NMR (400 MHz, DMSO-d6) δ 11.66 (s, 1H), 8.98 (s, 1H), 8.53-8.51 (d, J=8.4 Hz, 1H), 8.00-7.98 (d, J=7.0 Hz, 2H), 7.68-7.61 (m, 3H), 7.53-7.51 (d, J=8.3 Hz, 1H), 7.36-7.34 (d, J=8.1 Hz, 1H), 7.23-7.22 (d, J=1.8 Hz, 1H), 7.12-7.10 (dd, J=1.8 Hz, J=10.0 Hz, 1H), 4.27 (s, 2H), 3.80 (s, 3H). [M+Na]+: 415.2
    • Example 50 N-(7-(3-chloro-2-fluorophenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00055
  • 1H NMR (400 MHz, DMSO-d6) δ 11.70 (s, 1H), 9.07 (s, 1H), 8.59-8.57 (d, J=8.4 Hz, 1H), 8.00-7.99 (d, J=7.0 Hz, 2H), 7.69-7.61 (m, 5H), 7.59-7.56 (t, J=7.9 Hz, 1H), 7.37-7.33 (t, J=8.0 Hz, 1H), 4.42 (s, 2H). [M+H]+: 381.3.
    • Example 51 N-(3-oxo-7-(thiazol-5-yl)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00056
  • 1H NMR (400 MHz, DMSO-d6) δ 11.74 (s, 1H), 9.24 (s, 1H), 9.19 (s, 1H), 8.58-8.55 (d, J=8.4 Hz, 1H), 8.29 (s, 1H), 7.99-7.98 (d, J=8.0 Hz, 2H), 7.94-7.92 (d, J=8.4 Hz, 1H), 7.68-7.61 (m, 3H), 4.68 (s, 2H). [M+H]+: 336.0.
    • Example 52 N-(3-oxo-7-(thiazol-4-yl)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00057
  • 1H NMR (400 MHz, DMSO-d6) δ 11.79 (s, 1H), 9.28 (s, 1H), 9.16 (s, 1H), 8.59-8.57 (d, J=8.6 Hz, 1H), 8.26-8.24 (d, J=8.5 Hz, 1H), 8.17 (s, 1H), 8.00-7.98 (d, J=7.6 Hz, 2H), 7.68-7.63 (m, 3H), 4.76 (s, 2H). [M+H]+: 336.1.
    • Example 53 N-(3-oxo-7-(thiazol-2-yl)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00058
  • 1H NMR (400 MHz, DMSO-d6) δ 11.81 (s, 1H), 9.22 (s, 1H), 8.62-8.60 (d, J=8.5 Hz, 1H), 8.21-8.19 (d, J=8.6 Hz, 1H), 8.01-7.99 (m, 3H), 7.86-7.85 (d, J=3.2 Hz, 1H), 7.69-7.62 (m, 3H), 4.77 (s, 2H). [M+H]+: 336.1
    • Example 54 N-(7-(1H-imidazol-4-yl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00059
  • 1H NMR (400 MHz, DMSO-d6) δ 11.75 (s, 1H), 8.91 (s, 1H), 8.44-8.42 (d, J=8.0 Hz, 1H), 8.20 (s, 1H), 8.04-7.97 (m, 3H), 7.66-7.62 (m, 4H), 4.51 (s, 2H). [M+H]+: 319.0.
    • Example 55 N-(3-oxo-7-(1H-pyrazol-4-yl)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00060
  • 1H NMR (400 MHz, DMSO-d6) δ 11.75 (s, 1H), 8.91 (s, 1H), 8.43-8.41 (d, J=8.0 Hz, 1H), 8.22 (s, 2H), 8.03-7.97 (m, 3H), 7.68-7.60 (m, 4H), 4.51 (s, 2H). [M+H]+: 319.2.
    • Example 56 N-(7-(1-methyl-1H-imidazol-5-yl)-3-oxoisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00061
  • 1H NMR (400 MHz, DMSO-d6) δ 11.66 (s, 1H), 9.09 (s, 1H), 8.58-8.56 (d, J=8.0 Hz, 1H), 8.01-7.98 (m, 2H), 7.77 (s, 1H), 7.71-7.61 (m, 4H), 7.21 (s, 1H), 4.48 (s, 2H), 3.65 (s, 2H). [M+H]+: 333.1
    • Example 57 N-(7-(1-methyl-1H-pyrazol-4-yl)-3-oxoisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00062
  • 1H NMR (400 MHz, DMSO-d6) δ 11.74 (s, 1H), 8.88 (s, 1H), 8.44-8.41 (d, J=8.4 Hz, 1H), 8.18 (s, 2H), 8.04-7.97 (m, 3H), 7.68-7.60 (m, 3H), 4.51 (s, 2H). [M+H]+: 333.1
    • Example 58 N-(3-oxo-7-(1H-1,2,4-triazol-5-yl)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00063
  • 1H NMR (400 MHz, DMSO-d6) δ 11.4 (s, 1H), 8.90 (s, 1H), 8.44-8.42 (d, J=8.2 Hz, 1H), 8.21 (s, 2H), 8.04-8.02 (d, J=8.2 Hz, 1H), 7.99-7.97 (d, J=7.2 Hz, 2H), 7.70-7.60 (m, 3H), 4.52 (s, 2H). [M+H]+: 319.0.
    • Example 59 N-(7-(1-methyl-1H-1,2,4-triazol-5-yl)-3-oxoisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00064
  • 1H NMR (400 MHz, DMSO-d6) δ 11.75 (s, 1H), 9.14 (s, 1H), 8.65-8.63 (d, J=8.4 Hz, 1H), 8.08 (s, 1H), 8.03-7.99 (m, 3H), 7.71-7.62 (m, 3H), 4.58 (s, 2H), 4.02 (s, 3H). [M+H]+: 334.0.
    • Preparation Example 2 Preparation of 7-amino-4-phenylisoindolin-1-one
  • Figure US20160311772A1-20161027-C00065
    • Step 1: Preparation of 7-nitro-4-phenylisoindolin-1-one (15)
  • To a stirred suspension solution of the key intermediate 5 (50.00 g, 194.5 mmol) in DME (1700 mL) was added phenylboronic acid (31.00 g, 254.2 mmol), Pd(OAc)2 (4.38 g, 19.5 mmol), Na2CO3 (41.30 g, 389.6 mmol) and H2O (425 mL). The mixture was degassed with N2 for three times, then stirred at 75° C. under N2 atmosphere for 3 hours; the reaction mixture was filtered through a Celite pad when it was hot; the precipitate was filtered to give the compound 15 (15.50 g) as a brown solid; and the filtrate was extracted with EtOAc (2×200 mL), washed with brine (300 mL), dried over anhydrous Na2SO4, and concentrated in vacuo to give the compound 15 (28 g, 110.1 mmol, 57%) as a yellow solid.
  • 1H NMR (400 MHz, DMSO-d6) δ 9.06 (s, 1H), 7.97-7.95 (d, J=8.12 Hz, 1H), 7.83-7.81 (d, J=8.12 Hz, 1H), 7.67-7.65 (m, 2H), 7.56-7.47 (m, 3H), 4.57 (s, 2H). [M+H]+; 255.
    • Step 2: Preparation of 7-amino-4-phenylisoindolin-1-one (16)
  • Figure US20160311772A1-20161027-C00066
  • To a stirred suspension solution of the compound 15 (10.00 g, 39.3 mmol) in THF (500 mL) was added 10% Pd/C (1.50 g). The reaction mixture was degassed with H2 three times, and then stirred at 45° C. under N2 atmosphere overnight. After TLC showed the reaction was completed, the reaction mixture was cooled to room temperature, and filtered through a Celite pad. The filtrate was concentrated in vacuo to give the crude solid; then EtOAc (150 mL) was added thereto and the resulting mixture was stirred for 10 min, and filtered to give the pure title compound 16 (7.50 g, 33.4 mmol, 85%) as a light yellow solid.
  • 1H NMR (400 MHz, DMSO-d6) δ 8.24 (s, 1H), 7.49-7.47 (m, 2H), 7.43-7.39 (m, 2H), 7.33-7.26 (m, 2H), 6.69-6.67 (d, J=8.32 Hz, 1H), 6.21 (s, 1H), 4.40 (s, 2H). [M+H]+: 225.
  • The following compounds of Examples 60 to 86 were obtained by using corresponding starting materials and repeating the procedure of Preparation Example 2.
    • Example 60 7-Amino-4-(4-methoxyphenyl)isoindolin-1-one
  • Figure US20160311772A1-20161027-C00067
  • 1H NMR (400 MHz, DMSO-d6) δ 8.23 (s, 1H), 7.40 (d, J=8.8 Hz, 2H), 7.26 (d, J=8.4 Hz, 1H), 6.97 (d, J=8.8 Hz, 2H), 6.65 (d, J=8.0 Hz, 1H), 6.15 (s, 2H), 4.37 (s, 2H), 3.78 (s, 3H). [M+H]+: 255.
    • Example 61 7-Amino-4-(4-fluorophenyl)isoindolin-1-one
  • Figure US20160311772A1-20161027-C00068
  • 1H NMR (400 MHz, DMSO-d6) δ 8.95 (d, J=2.0 Hz, 1H), 8.74 (s, 1H), 8.52 (s, 1H), 7.57 (dd, J=5.2, 8.8 Hz, 2H), 7.50 (d, J=8.0 Hz, 1H), 7.26 (t, J=8.8 Hz, 2H), 7.11 (d, J=8.4 Hz, 1H), 6.15 (s, 2H), 4.46 (s, 2H). [M+H]+: 243.
    • Example 62 7-Amino-4-(4-chlorophenyl)isoindolin-1-one
  • Figure US20160311772A1-20161027-C00069
  • 1H NMR (400 MHz, DMSO-d6) δ 8.30 (s, 1H), 7.51 (d, J=8.4 Hz, 2H), 7.44 (d, J=8.4 Hz, 2H), 7.33 (d, J=8.4 Hz, 1H), 6.67 (d, J=8.4 Hz, 1H), 6.28 (s, 2H), 4.40 (s, 2H). [M+H]+: 259.
    • Example 63 7-Amino-4-(p-tolyl)isoindolin-1-one
  • Figure US20160311772A1-20161027-C00070
  • 1H NMR (400 MHz, CDCl3) δ 7.35-7.22 (m, 4H), 6.69 (d, J=7.6 Hz, 1H), 5.97 (d, J=7.6 Hz, 1H), 4.47 (s, 2H), 2.40 (s, 3H). [M+H]+: 239.
    • Example 64 4-(4-Acetylphenyl)-7-aminoisoindolin-1-one
  • Figure US20160311772A1-20161027-C00071
  • 1H NMR (400 MHz, DMSO-d6) δ 8.34 (s, 1H), 7.98 (d, J=8.4 Hz, 2H), 7.64 (d, J=8.4 Hz, 2H), 7.43 (d, J=8.4 Hz, 1H), 6.70 (d, J=8.0 Hz, 1H), 6.28 (s, 2H), 4.47 (s, 2H), 2.59 (s, 3H). [M+H]+: 267.
    • Example 65 7-Amino-4-(pyridin-4-yl)isoindolin-1-one
  • Figure US20160311772A1-20161027-C00072
  • 1H NMR (400 MHz, CDCl3) δ 8.64 (d, J=6.0 Hz, 2H), 7.43 (d, J=8.4 Hz, 1H), 7.32 (d, J=6.0 Hz, 2H), 6.71 (d, J=8.4 Hz, 1H), 6.06 (s, 1H), 5.49 (s, 2H), 4.64 (s, 2H). [M+H]+: 226.
    • Example 66 7-Amino-4-(2,6-dichloropyrimidin-4-yl)isoindolin-1-one
  • Figure US20160311772A1-20161027-C00073
  • 1H NMR (400 MHz, DMSO-d6) δ 8.46 (s, 1H), 8.13-8.11 (m, 2H), 7.03 (s, 2H), 6.71 (d, J=8.8 Hz, 1H), 4.65 (s, 2H). [M+H]+: 296.
    • Example 67 7-Amino-4-(2-chloropyrimidin-4-yl)isoindolin-1-one
  • Figure US20160311772A1-20161027-C00074
  • 1H NMR (400 MHz, DMSO-d6) δ 8.63 (d, J=5.6 Hz, 1H), 8.45 (s, 1H), 8.06 (d, J=8.8 Hz, 1H), 7.90 (d, J=5.6 Hz, 1H), 6.92 (s, 2H), 6.72 (d, J=8.8 Hz, 1H), 4.66 (s, 2H). [M+H]+: 261.
    • Example 68 7-Amino-4-(2-((3-methoxyphenyl)amino)pyridin-4-yl) isoindolin-1-one
  • Figure US20160311772A1-20161027-C00075
  • 1H NMR (400 MHz, DMSO-d6) δ 9.01 (s, 1H), 8.39 (s, 1H), 8.14 (d, J=5.2 Hz, 1H), 7.46-7.44 (m, 2H), 7.21-7.13 (m, 2H), 6.91-6.90 (m, 2H), 6.70 (d, J=8.4 Hz, 1H), 6.46 (d, J=6.8 Hz, 1H), 6.41 (s, 2H), 4.48 (s, 2H), 3.73 (s, 3H). [M+H]+: 347.
    • Example 69 7-Amino-4-(4-((3-methoxyphenyl)amino)pyridin-2-yl) isoindolin-1-one
  • Figure US20160311772A1-20161027-C00076
  • 1H NMR (400 MHz, DMSO-d6) δ 8.79 (s, 1H), 8.28 (s, 1H), 8.23 (d, J=5.6 Hz, 1H), 7.68 (d, J=8.4 Hz, 1H), 7.25 (t, J=8.0 Hz, 1H), 7.20 (d, J=2.4 Hz, 1H), 6.82-6.81 (m, 2H), 6.74 (t, J=2.0 Hz, 1H), 6.66 (d, J=8.8 Hz, 1H), 6.62-6.60 (m, 1H), 6.39 (s, 2H), 4.58 (s, 2H), 3.75 (s, 3H). [M+H]+: 347.
    • Example 70 7-Amino-4-(2-((3-methoxyphenyl)amino)pyrimidin-4-yl) isoindolin-1-one
  • Figure US20160311772A1-20161027-C00077
  • 1H NMR (400 MHz, DMSO-d6) δ 9.36 (s, 1H), 8.46 (s, 1H), 8.42 (d, J=5.6 Hz, 1H), 7.94 (d, J=8.4 Hz, 1H), 7.45 (br.s, 1H), 7.32 (d, J=7.6 Hz, 1H), 7.19-7.17 (m, 2H), 6.70-6.68 (m, 3H), 6.55-6.52 (m, 1H), 4.72 (s, 2H), 3.74 (s, 3H). [M+H]+: 348.
    • Example 71 7-Amino-4-(2-(1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl) isoindolin-1-one
  • Figure US20160311772A1-20161027-C00078
  • 1H NMR (400 MHz, DMSO-d6) δ 9.15 (s, 1H), 8.47 (s, 1H), 8.35 (d, J=5.2 Hz, 1H), 7.91 (d, J=8.4 Hz, 1H), 7.88 (br.s, 1H), 7.47 (s, 1H), 7.07 (d, J=5.6 Hz, 1H), 6.69-6.66 (m, 3H), 4.67 (s, 2H), 3.81 (s, 3H). [M+H]+: 322.
    • Example 72 7-Amino-4-(2-(phenylamino)pyrimidin-4-yl)isoindolin-1-one
  • Figure US20160311772A1-20161027-C00079
  • 1H NMR (400 MHz, DMSO-d6) δ 9.36 (s, 1H), 8.44 (s, 1H), 8.41 (d, J=5.2 Hz, 1H), 7.93 (d, J=8.8 Hz, 1H), 7.72 (d, J=8.0 Hz, 2H), 7.29 (t, J=8.0 Hz, 2H), 7.18 (d, J=5.2 Hz, 1H), 6.97-6.93 (m, 1H), 6.70-6.67 (m, 3H), 4.70 (s, 2H). [M+H]+: 318.
    • Example 73 7-Amino-4-(2-((3-fluorophenyl)amino)pyrimidin-4-yl) isoindolin-1-one
  • Figure US20160311772A1-20161027-C00080
  • 1H NMR (400 MHz, DMSO-d6) δ 9.59 (s, 1H), 8.48 (s, 1H), 8.46 (d, J=5.6 Hz, 1H), 7.95 (d, J=8.8 Hz, 1H), 7.79 (d, J=12.8 Hz, 1H), 7.51-7.48 (m, 1H), 7.31 (d, J=7.2 Hz, 1H), 7.24 (d, J=5.2 Hz, 1H), 6.75-6.74 (m, 1H), 6.71-6.68 (m, 3H), 4.73 (s, 2H). [M+H]+: 336.
    • Example 74 7-Amino-4-(2-((4-fluorophenyl)amino)pyrimidin-4-yl) isoindolin-1-one
  • Figure US20160311772A1-20161027-C00081
  • 1H NMR (400 MHz, DMSO-d6) δ 9.38 (s, 1H), 8.43 (s, 1H), 8.39 (d, J=5.2 Hz, 1H), 7.93 (d, J=8.8 Hz, 1H), 7.73-7.69 (m, 2H), 7.19-7.11 (m, 3H), 6.69-6.67 (m, 3H), 4.68 (s, 2H). [M+H]+: 336.
    • Example 75 7-Amino-4-(2-((4-methoxyphenyl)amino)pyrimidin-4-yl) isoindolin-1-one
  • Figure US20160311772A1-20161027-C00082
  • 1H NMR (400 MHz, DMSO-d6) δ 9.16 (s, 1H), 8.43 (s, 1H), 8.35 (d, J=5.2 Hz, 1H), 7.91 (d, J=8.8 Hz, 1H), 7.57 (d, J=8.8 Hz, 2H), 7.12 (d, J=5.6 Hz, 1H), 6.89 (d, J=9.2 Hz, 2H), 6.68 (d, J=8.4 Hz, 1H), 6.65 (s, 2H), 4.65 (s, 2H), 3.74 (s, 3H). [M+H]+: 348.
    • Example 76 N-(4-((4-(7-amino-1-oxoisoindolin-4-yl)pyrimidin-2-yl)amino) phenyl)acetamide
  • Figure US20160311772A1-20161027-C00083
  • 1H NMR (400 MHz, DMSO-d6) δ 9.82 (s, 1H), 9.28 (s, 1H), 8.44 (s, 1H), 8.38 (d, J=5.2 Hz, 1H), 7.92 (d, J=8.4 Hz, 1H), 7.61 (d, J=8.8 Hz, 2H), 7.48 (d, J=8.8 Hz, 2H), 7.15 (d, J=5.2 Hz, 1H), 6.69-6.67 (m, 3H), 4.68 (s, 2H), 2.01 (s, 3H). [M+H]+: 375.
    • Example 77 N-(3-((4-(7-amino-1-oxoisoindolin-4-yl)pyrimidin-2-yl)amino) phenyl)acetamide
  • Figure US20160311772A1-20161027-C00084
  • 1H NMR (400 MHz, DMSO-d6) δ 9.87 (s, 1H), 9.38 (s, 1H), 8.44 (s, 1H), 8.39 (d, J=5.2 Hz, 1H), 797-7.94 (m, 2H), 7.38 (d, J=6.8 Hz, 1H), 7.19-7.16 (m, 3H), 6.69-6.67 (m, 3H), 4.70 (s, 2H), 2.03 (s, 3H). [M+H]+: 375.
    • Example 78 7-Amino-4-(6-((3-methoxyphenyl)amino)pyrimidin-4-yl) isoindolin-1-one
  • Figure US20160311772A1-20161027-C00085
  • 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 8.63 (s, 1H), 8.41 (s, 1H), 7.84 (d, J=8.8 Hz, 1H), 7.41 (s, 1H), 7.23 (d, J=4.8 Hz, 2H), 7.01 (s, 1H), 6.70 (d, J=8.4 Hz, 1H), 6.62 (s, 2H), 6.60-6.57 (m, 1H), 4.64 (s, 2H), 3.75 (s, 3H). [M+H]+: 348.
    • Example 79 7-Amino-4-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl) isoindolin-1-one
  • Figure US20160311772A1-20161027-C00086
  • 1H NMR (400 MHz, DMSO-d6) δ 11.90 (s, 1H), 8.54 (d, J=2.0 Hz, 1H), 8.26 (s, 1H), 8.20 (d, J=2.0 Hz, 1H), 7.74-7.71 (m, 3H), 7.59 (d, J=8.0 Hz, 1H), 7.47 (t, J=7.6 Hz, 2H), 7.35 (t, J=7.6 Hz, 1H), 6.71 (d, J=8.4 Hz, 1H), 6.12 (s, 2H), 4.42 (s, 2H) [M+H]+: 341.
    • Example 80 7-Amino-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)isoindolin-1-one
  • Figure US20160311772A1-20161027-C00087
  • 1H NMR (400 MHz, DMSO-d6) δ 11.70 (s, 1H), 8.26 (s, 1H), 8.19 (d, J=4.8 Hz, 1H), 7.48 (d, J=8.4 Hz, 1H), 7.47-7.46 (m, 1H), 7.12 (d, J=5.2 Hz, 1H), 6.73 (d, J=8.4 Hz, 1H), 6.38 (d, J=3.2 Hz, 1H), 6.35 (s, 2H), 4.34 (s, 2H). [M+H]+: 265.
    • Example 81 7-Amino-4-(2-(4-methylpiperazin-1-yl)pyrimidin-4-yl) isoindolin-1-one
  • Figure US20160311772A1-20161027-C00088
  • 1H NMR (400 MHz, DMSO-d6) δ 8.35 (s, 1H), 8.30 (d, J=5.6 Hz, 1H), 7.92 (d, J=8.4 Hz, 1H), 7.05 (d, J=5.6 Hz, 1H), 6.68-6.66 (m, 3H), 4.68 (s, 2H), 3.75 (t, J=4.8 Hz, 4H), 2.38 (t, J=4.8 Hz, 4H), 2.22 (s, 3H). [M+H]+: 325.
    • Example 82 7-Amino-4-(2-morpholinopyrimidin-4-yl)isoindolin-1-one
  • Figure US20160311772A1-20161027-C00089
  • 1H NMR (400 MHz, DMSO-d6) δ 8.35 (s, 1H), 8.33 (d, J=5.2 Hz, 1H), 7.94 (d, J=8.8 Hz, 1H), 7.10 (d, J=5.2 Hz, 1H), 6.68-6.66 (m, 3H), 4.69 (s, 2H), 3.72-3.70 (m, 8H). [M+H]+: 312.
    • Example 83 7-Amino-4-(2-(p-tolylamino)pyrimidin-4-yl)isoindolin-1-one
  • Figure US20160311772A1-20161027-C00090
  • 1H NMR (400 MHz, DMSO-d6) δ 9.25 (s, 1H), 8.43 (s, 1H), 8.38 (d, J=5.2 Hz, 1H), 7.92 (d, J=8.8 Hz, 1H), 7.58 (d, J=8.0 Hz, 2H), 7.15 (d, J=5.6 Hz, 1H), 7.10 (d, J=8.0 Hz, 2H), 6.68 (d, J=8.4 Hz, 1H), 6.66 (s, 2H), 4.68 (s, 2H), 2.26 (s, 3H). [M+H]+: 332.
    • Example 84 7-Amino-4-(2-(m-tolylamino)pyrimidin-4-yl)isoindolin-1-one
  • Figure US20160311772A1-20161027-C00091
  • 1H NMR (400 MHz, DMSO-d6) δ 9.30 (s, 1H), 8.46 (s, 1H), 8.40 (d, J=5.2 Hz, 1H), 7.93 (d, J=8.8 Hz, 1H), 7.62-7.49 (m, 3H), 7.19-7.15 (m, 2H), 6.78 (d, J=8.0 Hz, 1H), 6.68 (d, J=8.0 Hz, 1H), 6.67 (s, 2H), 4.69 (s, 2H), 2.29 (s, 3H). [M+H]+: 332.
    • Example 85 N-(4-(3-(7-amino-1-oxoisoindolin-4-yl)-1H-pyrrolo[2,3-b]pyridine-5-yl)phenyl)acetamide
  • Figure US20160311772A1-20161027-C00092
  • 1H NMR (400 MHz, DMSO-d6) δ 11.86 (s, 1H), 10.02 (s, 1H), 8.52 (s, 1H), 8.26 (d, J=5.2 Hz, 1H), 8.17 (d, J=8.8 Hz, 1H), 7.67-7.65 (m, 3H), 7.57 (d, J=8.0 Hz, 1H), 6.72-6.70 (m, 2H), 6.12 (s, 2H), 4.41 (s, 2H), 2.06 (s, 3H). [M+H]+: 398.
    • Example 86 7-Amino-4-(5-(5-(morpholinomethyl)thiophen-2-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)isoindolin-1-one
  • Figure US20160311772A1-20161027-C00093
  • 1H NMR (400 MHz, DMSO-d6) δ 11.93 (s, 1H), 8.54 (d, J=2.4 Hz, 1H), 8.27 (s, 1H), 8.13 (d, J=2.0 Hz, 1H), 7.70 (d, J=2.4 Hz, 1H), 7.53 (d, J=8.0 Hz, 1H), 7.37 (d, J=3.6 Hz, 1H), 6.97 (d, J=3.6 Hz, 1H), 6.73 (d, J=8.4 Hz, 1H), 6.13 (s, 2H), 4.40 (s, 2H), 3.67 (s, 2H), 3.58 (t, J=4.8 Hz, 4H), 2.42 (t, J=4.8 Hz, 4H). [M+H]+: 446.
    • Example 87 2-Methyl-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00094
  • To a stirred solution of the compound 16 (200 mg, 0.89 mmol) in THF (30 mL) was added NMM (541 mg, 5.35 mmol) at 0° C., and the mixture was stirred for 10 min. Then, 2-Methylbenzoyl chloride (414 mg, 2.68 mmol) was added dropwise to the mixture, which was then stirred at room temperature for 2 hours. After TLC showed the reaction was completed, the reaction mixture was poured into water (50 mL), extracted with EtOAc (2×100 mL), washed with brine (200 mL), dried over anhydrous Na2SO4, and concentrated in vacuo to give the crude product, which was purified by column chromatography to give the compound 17 (205 mg, 0.60 mmol, 67%) as a white solid.
  • 1H NMR (400 MHz, DMSO-d6) δ 11.10 (s, 1H), 9.00 (s, 1H), 8.58-8.56 (d, J=8.44 Hz, 1H), 7.72-7.70 (d, J=8.44 Hz, 1H), 7.63-7.61 (m, 3H), 7.52-7.45 (m, 3H), 7.42-7.35 (m, 3H), 4.57 (s, 2H), 2.51-2.49 (m, 3H). [M+H]+: 343.
  • The following compounds of Examples 88 to 92 were obtained by using corresponding starting materials and repeating the procedure of Example 1.
    • Example 88 3-Methyl-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00095
  • 1H NMR (400 MHz, DMSO-d6) δ 11.71 (s, 1H), 9.06 (s, 1H), 8.59-8.57 (d, J=8.40 Hz, 1H), 7.81-7.77 (m, 2H), 7.72-7.70 (d, J=8.40 Hz, 1H), 7.63-7.61 (m, 2H), 7.53-7.48 (m, 4H), 7.42-7.39 (t, J=7.28 Hz, 1H), 4.60 (s, 1H), 2.43 (s, 3H). [M+H]+: 343.
    • Example 89 4-Methyl-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00096
  • 1H NMR (400 MHz, DMSO-d6) δ 11.69 (s, 1H), 9.06 (s, 1H), 8.58-8.56 (d, J=8.44 Hz, 1H), 7.89-7.87 (m, 2H), 7.71-7.69 (d, J=8.44 Hz, 1H), 7.63-7.61 (m, 2H), 7.51-7.47 (m, 2H), 7.43-7.38 (m, 3H), 4.60 (s, 2H), 2.42 (s, 2H). [M+H]+: 343.
    • Example 90 3-Chloro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00097
  • 1H NMR (400 MHz, DMSO-d6) δ 11.74 (s, 1H), 9.10 (s, 1H), 8.54-8.52 (d, J=8.40 Hz, 1H), 7.97 (s, 1H), 7.94-7.92 (d, J=7.76 Hz, 1H), 7.77-7.72 (m, 2H), 7.52-7.48 (m, 2H), 7.43-7.41 (d, J=7.40 Hz, 1H), 4.61 (s, 1H). [M+H]+: 363.
    • Example 91 2,4-Difluoro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00098
  • 1H NMR (400 MHz, DMSO-d6) δ 11.55-11.53 (d, J=6.84 Hz, 1H), 8.99 (s, 1H), 8.63-8.61 (d, J=8.48 Hz, 1H), 8.10-8.03 (m, 1H), 7.72-7.70 (d, J=8.48 Hz, 1H), 7.63-7.61 (m, 2H), 7.56-7.48 (m, 3H), 7.43-7.39 (m, 1H), 7.34-7.30 (t, J=8.44 Hz, 1H), 4.57 (s, 2H). [M+H]+: 365.
    • Example 92 3,4-Difluoro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00099
  • 1H NMR (400 MHz, DMSO-d6) δ 11.72 (s, 1H), 9.11 (s, 1H), 8.52-8.50 (d, J=8.40 Hz, 1H), 7.98-7.93 (t, J=10.20 Hz, 1H), 7.83 (m, 1H), 7.76-7.69 (m, 2H), 7.63-7.61 (m, 2H), 7.51-7.48 (m, 2H), 7.43-7.39 (d, J=7.28 Hz, 1H), 4.61 (s, 2H). [M+H]+: 365.
    • Example 93 3,4-Dimethyl-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00100
  • To a stirred solution of 3,4-dimethylbenzoic acid (502 mg, 3.34 mmol) in DCM (35 mL) was added oxalyl chloride (509 mg, 4.01 mmol) dropwise at 0° C. under N2 atmosphere. After TLC showed the reaction was completed, the reaction mixture was added to a solution of 7-amino-4-phenylisoindolin-1-one 16 (250 mg, 1.11 mmol) in THF (25 mL) at 0° C. for 5 min, and then TEA (1354 mg, 13.38 mmol) was added dropwise over 5 min. The reaction mixture was then stirred at room temperature for 2 hours. After TLC showed the reaction was completed, the mixture was poured into water (50 mL), extracted with EtOAc (2×200 mL), washed with brine (200 mL), dried over anhydrous Na2SO4, and concentrated to give the crude residue, which was purified by column chromatography to give the title product (140 mg, 0.39 mmol, 35%) as a white solid.
  • 1H NMR (400 MHz, DMSO-d6) δ 11.68 (s, 1H), 9.05 (s, 1H), 8.58-8.56 (d, J=8.40 Hz, 1H), 7.77 (s, 1H), 7.72-7.70 (m, 2H), 7.63-7.61 (m, 2H), 7.51-7.47 (m, 2H), 7.42-7.37 (m, 2H), 4.60 (s, 2H), 2.34-2.33 (m, 6H). [M+H]+: 357.
  • The following compounds of Examples 94 to 105 were obtained by using corresponding starting materials and repeating the procedure of Example 93.
    • Example 94 2-(Dimethylamino)-N-(3-oxo-7-phenylisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00101
  • 1H NMR (400 MHz, DMSO-d6) δ 12.58 (s, 1H), 8.81-8.78 (m, 2H), 7.87-7.85 (d, J=7.72 Hz, 1H), 7.67-7.65 (d, J=8.52 Hz, 1H), 7.61-7.60 (m, 2H), 7.52-7.47 (m, 3H), 7.42-7.38 (m, 1H), 7.28-7.26 (d, J=8.00 Hz, 1H), 7.16-7.12 (m, 1H), 4.53 (s, 2H), 2.77 (s, 6H). [M+H]+: 372.
    • Example 95 3-(Dimethylamino)-N-(3-oxo-7-phenylisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00102
  • 1H NMR (400 MHz, DMSO-d6) δ 11.72 (s, 1H), 9.06 (s, 1H), 8.58-8.56 (d, J=8.44 Hz, 1H), 7.72-7.70 (d, J=8.44 Hz, 1H), 7.63-7.61 (m, 2H), 7.51-7.48 (m, 2H), 7.42-7.40 (m, 2H), 7.30 (s, 1H), 7.25-7.23 (d, J=7.60 Hz, 1H), 7.01-6.99 (d, J=8.24 Hz, 1H), 4.60 (s, 2H), 3.00 (s, 6H). [M+H]+: 372.
    • Example 96 2-(Methylthio)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00103
  • 1H NMR (400 MHz, DMSO-d6) δ 11.20 (s, 1H), 9.01 (s, 1H), 8.54-8.52 (d, J=8.40 Hz, 1H), 7.73-7.70 (d, J=8.44 Hz, 1H), 7.68-7.66 (d, J=7.56 Hz, 1H), 7.63-7.61 (m, 2H), 7.59-7.54 (m, 1H), 7.52-7.48 (m, 3H), 7.42-7.39 (m, 1H), 7.35-7.31 (m, 1H), 4.58 (s, 2H), 2.46 (s, 3H). [M+H]+: 375.
    • Example 97 3-(Methylthio)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00104
  • 1H NMR (400 MHz, DMSO-d6) δ 11.76 (s, 1H), 9.10 (s, 1H), 8.56-8.54 (d, J=8.40 Hz, 1H), 7.83 (s, 1H), 7.74-7.71 (m, 2H), 7.63-7.62 (m, 2H), 7.56-7.55 (m, 2H), 7.52-7.48 (m, 2H), 7.42-7.39 (m, 1H), 4.61 (s, 2H), 2.58 (s, 3H). [M+H]+: 375.
    • Example 98 2-(Methylsulfonyl)-N-(3-oxo-7-phenylisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00105
  • 1H NMR (400 MHz, DMSO-d6) δ 11.08 (s, 1H), 9.03 (s, 1H), 8.50-8.48 (d, J=8.40 Hz, 1H), 8.10-8.08 (d, J=7.80 Hz, 1H), 7.95-7.90 (m, 1H), 7.87-7.82 (m, 2H), 7.74-7.72 (d, J=8.40 Hz, 1H), 7.63-7.61 (m, 2H), 7.52-7.48 (m, 2H), 7.43-7.40 (m, 1H), 4.58 (s, 2H), 3.43 (s, 3H). [M+H]+: 407.
    • Example 99 3-(Methylsulfonyl)-N-(3-oxo-7-phenylisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00106
  • 1H NMR (400 MHz, DMSO-d6) δ 11.86 (s, 1H), 9.10 (s, 1H), 8.56-8.54 (d, J=8.40 Hz, 1H), 8.50 (s, 1H), 8.30-8.28 (d, J=7.96 Hz, 1H), 8.23-8.21 (d, J=8.40 Hz, 1H), 7.95-7.91 (m, 1H), 7.76-7.73 (d, J=8.40 Hz, 1H), 7.64-7.62 (m, 2H), 7.52-7.48 (m, 2H), 7.43-7.39 (m, 1H), 4.62 (s, 2H), 3.32 (S, 3H). [M+H]+: 407.
    • Example 100 4-(Methylsulfonyl)-N-(3-oxo-7-phenylisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00107
  • 1H NMR (400 MHz, DMSO-d6) δ 11.81 (s, 1H), 9.10 (s, 1H), 8.56-8.54 (d, J=8.40 Hz, 1H), 8.21-8.04 (m, 5H), 7.75-7.73 (d, J=8.44 Hz, 1H), 7.64-7.62 (m, 2H), 7.52-7.48 (m, 2H), 7.43-7.39 (m, 1H), 4.61 (s, 2H). [M+H]+: 407.
    • Example 101 2,4-Dimethoxy-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00108
  • 1H NMR (400 MHz, DMSO-d6) δ 12.10 (s, 1H), 8.82-8.80 (m, 2H), 8.06-8.04 (d, J=8.52 Hz, 1H), 7.66-7.60 (m, 3H), 7.50-7.47 (m, 2H), 7.41-7.37 (m, 1H), 6.73-6.70 (m, 2H), 4.54 (s, 2H), 4.08 (s, 3H), 3.87 (s, 3H). [M+H]+: 389.
    • Example 102 3,4-Dimethoxy-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00109
  • 1H NMR (400 MHz, DMSO-d6) δ 11.70 (s, 1H), 9.06 (s, 1H), 8.56-8.54 (d, J=8.40 Hz, 1H), 7.72-7.70 (d, J=8.44 Hz, 1H), 7.63-7.55 (m, 4H), 7.51-7.47 (m, 2H), 7.42-7.38 (m, 1H), 7.19-7.17 (d, J=8.44 Hz, 1H), 4.60 (s, 2H), 3.87 (s, 6H). [M+H]+: 389.
    • Example 103 2,4-Dichloro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00110
  • 1H NMR (400 MHz, DMSO-d6) δ 11.14 (s, 1H), 9.03 (s, 1H), 8.52-8.50 (d, J=8.36 Hz, 1H), 7.84-7.84 (d, J=1.96 Hz, 1H), 7.80-7.78 (d, J=8.28 Hz, 1H), 7.74-7.72 (d, J=8.40 Hz, 1H), 7.65-7.61 (m, 3H), 7.52-7.48 (m, 2H), 7.43-7.41 (d, J=7.32 Hz, 1H), 4.58 (s, 2H). [M+H]+: 397.
    • Example 104 3,4-Dichloro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00111
  • 1H NMR (400 MHz, DMSO-d6) δ 11.74 (s, 1H), 9.10 (s, 1H), 8.51-8.49 (d, J=8.40 Hz, 1H), 8.14 (s, 1H), 7.92 (s, 2H), 7.74-7.72 (d, J=8.40 Hz, 1H), 7.63-7.61 (m, 2H), 7.52-7.48 (m, 2H), 7.43-7.39 (d, J=7.32 Hz, 1H), 4.61 (s, 2H). [M+H]+: 397.
    • Example 105 2,4-Dimethyl-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00112
  • 1H NMR (400 MHz, DMSO-d6) δ 11.09 (s, 1H), 8.99 (s, 1H), 8.58-8.55 (d, J=8.40 Hz, 1H), 7.71-7.69 (d, J=8.44 Hz, 1H), 7.62-7.60 (m, 2H), 7.54-7.47 (m, 3H), 7.42-7.38 (m, 1H), 7.19-7.17 (m, 1H), 4.57 (s, 2H), 2.47 (s, 3H), 2.35 (s, 3H). [M+H]+: 357.
    • Preparation Example 3 Preparation of 2-acetamido-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00113
    • Step 1: Preparation of 2-nitro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide (19)
  • To a stirred solution of compound 16 (400 mg, 1.78 mmol) in THF (80 mL) was added NMM (1082 mg, 10.70 mmol) at 0° C., and the mixture was stirred for 10 min. Then, 2-nitrobenzoyl chloride (993 mg, 5.35 mmol) was added dropwise to the mixture, which was then stirred at room temperature for 2 hours. After TLC showed the reaction was completed, the reaction mixture was poured into water (30 mL), extracted with EtOAc (2×200 mL), washed with brine (300 mL), dried over anhydrous Na2SO4, and concentrated in vacuo to give the crude residue, which was purified by column chromatography to give the title compound 19 (450 mg, 1.21 mmol, 67%) as a light yellow solid.
  • 1H NMR (400 MHz, DMSO-d6) δ 11.24 (s, 1H), 9.04 (s, 1H), 8.44-8.41 (d, J=8.36 Hz, 1H), 8.17-8.15 (d, J=8.04 Hz, 1H), 7.96-7.91 (m, 2H), 7.86-7.82 (m, 1H), 7.74-7.72 (d, J=8.40 Hz, 1H), 7.64-7.62 (m, 2H), 7.52-7.48 (m, 2H), 7.43-7.40 (m, 1H), 4.59 (s, 2H).
    • Step 2: Preparation of 2-amino-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide (20)
  • To a stirred suspension solution of 2-nitro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 19 (450 mg, 1.21 mmol) in THF (40 mL) was added 10% Pd/C (100 mg). The mixture was degassed with H2 three times, and then heated at 40° C. overnight. After TLC showed the reaction was completed, the mixture was filtered through a Celite pad, and the filtrate was concentrated to give the title compound 20 (340 mg, 0.99 mmol, 82%) as a yellow solid.
  • 1H NMR (400 MHz, DMSO-d6) δ 11.53 (s, 1H), 9.02 (s, 1H), 8.56-8.54 (d, J=8.48 Hz, 1H), 7.70-7.68 (d, J=8.44 Hz, 1H), 7.62-7.61 (m, 3H), 7.51-7.47 (m, 2H), 7.42-7.38 (m, 1H), 7.29-7.25 (m, 1H), 6.84-6.82 (d, J=8.04 Hz, 1H), 6.70 (s, 2H), 6.67-6.63 (m, 1H), 4.59 (s, 2H).
    • Step 3: Preparation of 2-acetamido-N-(3-oxo-7-phenylisoindolin-4-yl) benzamide (21)
  • To a stirred suspension solution of 2-amino-N-(3-oxo-7-phenylisoindolin-4-yl) benzamide 20 (150 mg, 0.44 mmol) in DCM (40 mL) was added TEA (89.1 mg, 0.88 mmol) at 0° C., and then acetyl chloride (51.9 mg, 0.66 mmol) was added dropwise to the mixture over 3 min. After TLC showed the reaction was completed, H2O (30 mL) was added, and the mixture was extracted with DCM (2×40 mL) The combined organic phase was washed with brine (100 mL), dried over Na2SO4, and concentrated in vacuo to give the crude residue, which was then purified by column chromatography to give the title compound 21 (90 mg, 0.23 mmol, 53%) as a yellow solid.
  • The following compounds of Examples 106 and 107 were obtained by using corresponding starting materials and repeating the procedure of Preparation Example 3.
    • Example 106 2-Acetamido-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00114
  • 1H NMR (400 MHz, DMSO-d6) δ 11.47 (s, 1H), 10.59 (s, 1H), 9.04 (s, 1H), 8.56-8.54 (d, J=8.44 Hz, 1H), 8.06-8.04 (d, J=8.20 Hz, 1H), 7.81-7.79 (m, 1H), 7.72-7.70 (d, J=8.40 Hz, 1H), 7.63-7.56 (m, 3H), 7.52-7.48 (m, 2H), 7.43-7.39 (m, 1H), 7.31-7.27 (m, 1H), 4.59 (s, 2H), 2.07 (s, 3H).
    • Example 107 3-Acetamido-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00115
  • 1H NMR (400 MHz, DMSO-d6) δ 11.69 (s, 1H), 10.23 (s, 1H), 9.08 (s, 1H), 8.59-8.57 (d, J=8.44 Hz, 1H), 8.23 (s, 1H), 7.90-7.88 (d, J=7.96 Hz, 1H), 7.73-7.71 (d, J=8.44 Hz, 1H), 7.64-7.61 (m, 3H), 7.56-7.48 (m, 3H), 7.43-7.39 (m, 1H), 4.61 (s, 2H), 2.09 (s, 3H).
    • Example 108 4-(Methylamino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00116
    • Step 1: Preparation of 4-((((9H-fluoren-9-yl)methoxy)carbonyl)(methyl) amino)benzoic acid (23)
  • Figure US20160311772A1-20161027-C00117
  • To a stirred suspension solution of 4-(methylamino)benzoic acid (1.00 g, 6.62 mmol) in 1,4-dioxane (10 mL) was added (9H-fluoren-9-yl)methyl carbonochloridate (2.05 g 7.94 mmol) as one portion at 0° C. The mixture was stirred for 10 min, and added with a solution of Na2CO3 (1.05 g, 9.092 mmol) in H2O (5 mL) The resulting mixture was stirred at room temperature overnight. After TLC showed the reaction was completed, the mixture was added with H2O (50 mL), adjusted to the pH of 7, extracted with EtOAc (2×100 mL), washed with brine (100 mL), dried over anhydrous Na2SO4, and concentrated in vacuo to give the crude residue, which was then purified by flash chromatography to give the title compound 23 (0.50 g, 1.34 mmol, 20%) as a white solid.
  • 1H NMR (400 MHz, DMSO-d6) δ 12.88 (s, 1H), 7.87-7.82 (m, 4H), 7.49-7.48 (m, 2H), 7.41-7.38 (m, 2H), 7.29-7.22 (m, 4H), 4.51-4.50 (m, 2H), 4.24 (m, 1H), 3.18 (s, 3H).
    • Step 2: Preparation of (9H-fluoren-9-yl)methylmethyl(4-((3-oxo-7-phenylisoindolin-4-yl)carbamoyl)phenyl)carbamate (25)
  • Figure US20160311772A1-20161027-C00118
  • To a stirred solution of the compound 23 (500 mg, 1.34 mmol) in DCM (30 mL) was added DMF (0.1 mL) at 0° C. Then, (COCl)2 (300 mg, 2.36 mmol) was added dropwise to the mixture over 5 min, and then the mixture was stirred at room temperature for 1 hour. After TLC showed the reaction was completed, the mixture was added dropwise to a suspension solution of 7-amino-4-phenylisoindolin-1-one 16 (208 mg, 0.93 mmol) in DCM (30 mL) at 0° C., followed by stirring them at room temperature overnight. After TLC showed the reaction was completed, H2O (50 mL) was added, and the resulting mixture was extracted with DCM (2×50 mL), washed with brine (50 mL), dried over anhydrous Na2SO4, and concentrated in vacuo to give the crude residue, which was purified by column chromatography to give the title compound 25 (120 mg, 0.21 mmol, 22%) as a white solid.
  • 1H NMR (400 MHz, DMSO-d6) δ 11.73 (s, 1H), 9.14 (s, 1H), 8.61-8.59 (d, J=8.44 Hz, 1H), 7.93-7.91 (m, 2H), 7.86-7.84 (m, 2H), 7.74-7.72 (d, J=8.44 Hz, 1H), 7.64-7.63 (m, 2H), 7.53-7.48 (m, 4H), 7.43-7.38 (m, 3H), 7.31-7.28 (m, 2H), 7.24-7.22 (m, 2H), 4.63 (s, 2H), 4.58-4.56 (m, 2H), 4.28-4.25 (m, 1H), 3.20 (s, 3H).
    • Step 3: Preparation of 4-(methylamino)-N-(3-oxo-7-phenylisoindolin-4-yl) benzamide (26)
  • Figure US20160311772A1-20161027-C00119
  • To a stirred solution of the compound 25 (120 mg, 0.21 mmol) in DMF (12 mL) was added piperidine (2.4 mL), and the mixture was stirred at room temperature overnight. After TLC showed the reaction was completed, the solution was concentrated in vacuo to give the crude residue, which was then purified by column chromatography to give the title compound 26 (50 mg, 0.14 mmol, 67%) as a white solid.
  • 1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 9.00 (s, 1H), 8.58-8.56 (d, J=8.48 Hz, 1H), 7.77-7.75 (m, 2H), 7.68-7.66 (m, J=8.44 Hz, 1H), 7.62-7.60 (m, 2H), 7.50-7.47 (m, 2H), 7.41-7.37 (m, 1H), 6.67-6.65 (m, 2H), 6.52-6.49 (m, 1H), 4.58 (s, 2H), 2.77-2.76 (m, 3H).
  • The following compounds of Examples 109 to 225 were obtained by using corresponding starting materials and repeating the procedure of Example 108.
    • Example 109 3-Methyl-N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide
  • Figure US20160311772A1-20161027-C00120
  • 1H NMR (400 MHz, DMSO-d6) δ 11.24 (s, 1H), 9.02 (s, 1H), 8.53 (d, J=8.5 Hz, 1H), 7.77 (d, J=5.0 Hz, 1H), 7.69 (d, J=8.4 Hz, 1H), 7.61 (d, J=7.3 Hz, 2H), 7.49 (t, J=7.5 Hz, 2H), 7.40 (t, J=7.6 Hz, 2H), 7.10 (d, J=5.0 Hz, 1H), 4.58 (s, 2H), 2.60 (s, 3H); MS (ESI) m/z 349 (M+H)+.
    • Example 110 4-Methyl-N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide
  • Figure US20160311772A1-20161027-C00121
  • 1H NMR (400 MHz, DMSO-d6) δ 11.58 (s, 1H), 9.07 (s, 1H), 8.45 (d, J=8.4 Hz, 1H), 7.61 (d, J=7.4 Hz, 2H), 7.56 (s, 2H), 7.49 (t, J=7.5 Hz, 2H), 7.41 (t, J=7.5 Hz, 1H), 4.60 (s, 2H), 2.30 (s, 3H); MS (ESI) m/z 349 (M+H)+.
    • Example 111 5-Methyl-N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide
  • Figure US20160311772A1-20161027-C00122
  • 1H NMR (400 MHz, DMSO-d6) δ 11.55 (s, 1H), 9.10 (s, 1H), 8.44 (d, J=8.4 Hz, 1H), 7.69 (d, J=8.4 Hz, 1H), 7.69 (d, J=8.4 Hz, 2H), 7.61 (d, J=7.3 Hz, 1H), 7.49 (t, J=7.5 Hz, 2H), 7.41 (t, J=7.5 Hz, 1H), 7.00 (dd, J=3.7, 0.94 Hz, 1H), 4.59 (s, 2H), 2.54 (s, 3H); MS (ESI) m/z 349 (M+H)+.
    • Example 112 N-(3-oxo-7-(o-tolyl)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00123
  • MS (ESI) m/z 343 (M+H)+.
  • 1H NMR (400 MHz, DMSO-d6) δ 11.63 (s, 1H), 8.98 (s, 1H), 8.55 (d, J=8.4 Hz, 1H), 8.02-7.99 (m, 2H), 7.70-7.62 (m, 3H), 7.49 (d, J=8.4 Hz, 1H), 7.38-7.27 (m, 4H), 4.22 (s, 2H), 2.16 (s, 3H); MS (ESI) m/z 343 (M+H)+.
    • Example 113 N-(3-oxo-7-(m-tolyl)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00124
  • MS (ESI) m/z 343 (M+H)+.
  • 1H NMR (400 MHz, DMSO-d6) δ 11.77 (s, 1H), 9.12 (s, 1H), 8.62 (d, J=8.4 Hz, 1H), 8.02-7.95 (m, 4H), 7.83-7.74 (m, 3H), 7.70-7.62 (m, 3H), 4.65 (s, 2H), 2.45 (s, 3H); MS (ESI) m/z 343 (M+H)+.
    • Example 114 N-(3-oxo-7-(2-(trifluoromethyl)phenyl)isoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00125
  • MS (ESI) m/z 397 (M+H)+.
  • 1H NMR (400 MHz, DMSO-d6) δ 11.60 (s, 1H), 9.02 (s, 1H), 8.54 (d, J=8.4 Hz, 1H), 8.02-8.00 (m, 2H), 7.92-7.90 (m, 1H), 7.80-7.75 (m, 1H), 7.71-7.63 (m, 4H), 7.58-7.55 (m, 1H), 7.48 (d, J=8.4 Hz, 1H), 4.32-4.29 (m, 1H), 4.02-3.98 (m, 1H); MS (ESI) m/z 397 (M+H)+.
    • Example 115 N-(3-oxo-7-(3-(trifluoromethyl)phenyl)isoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00126
  • MS (ESI) m/z 397 (M+H)+.
  • 1H NMR (400 MHz, DMSO-d6) δ 11.75 (s, 1H), 9.09 (s, 1H), 8.59 (d, J=8.4 Hz, 1H), 8.02-7.99 (m, 2H), 7.72-7.70 (m, 4H), 7.45-7.36 (m, 3H), 7.24-7.22 (m, 1H), 4.61 (s, 2H); MS (ESI) m/z 397 (M+H)+.
    • Example 116 4-Acetamido-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00127
  • 1H NMR (400 MHz, DMSO-d6) δ 10.84 (s, 1H), 10.38 (s, 1H), 8.76 (s, 1H), 8.06 (d, J=8.4 Hz, 2H), 7.80 (d, J=8.4 Hz, 2H), 7.58 (dd, J=8.4, 8.4 Hz, 3H), 7.47 (dd, J=7.6, 7.2 Hz, 2H), 7.44 (dd, J=7.2, 7.6 Hz, 1H), 7.25 (d, J=8.4 Hz, 1H), 4.55 (s, 2H), 2.11 (s, 3H). [M+H]+: 386.
    • Example 117 N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00128
  • 1H NMR (400 MHz, DMSO-d6) δ 11.75 (s, 1H), 9.10 (s, 1H), 8.58 (d, J=8.4 Hz, 1H), 8.00 (d, J=6.8 Hz, 2H), 7.73 (d, J=8.4 Hz, 1H), 7.67 (d, J=6.8 Hz, 1H), 7.65-7.62 (m, 4H), 7.50 (dd, J=7.2, 8.0 Hz, 2H), 7.40 (dd, J=7.6, 7.2 Hz, 1H), 4.61 (s, 2H). [M+H]+: 329.
    • Example 118 N-(7-(4-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00129
  • 1H NMR (400 MHz, DMSO-d6) δ 11.73 (s, 1H), 9.09 (s, 1H), 8.55 (d, J=8.4 Hz, 1H), 7.99 (d, J=6.8 Hz, 2H), 7.69-7.61 (m, 4H), 7.56 (d, J=8.8 Hz, 2H), 7.05 (d, J=8.8 Hz, 2H), 4.59 (s, 2H), 3.81 (s, 3H). [M+H]+: 359.
    • Example 119 4-Nitro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00130
  • 1H NMR (400 MHz, DMSO-d6) δ 11.87 (s, 1H), 9.16 (s, 1H), 8.56 (d, J=8.4 Hz, 1H), 8.47 (d, J=8.8 Hz, 2H), 8.21 (d, J=8.8 Hz, 2H), 7.75 (d, J=8.4 Hz, 1H), 7.64 (d, J=7.2 Hz, 2H), 7.50 (t, J=7.6 Hz, 2H), 7.42 (dd, J=7.6, 6.8 Hz, 1H), 4.63 (s, 2H). [M+H]+: 374.
    • Example 120 4-Acetamido-N-(7-(4-methoxyphenyl)-3-oxoisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00131
  • 1H NMR (400 MHz, DMSO-d6) δ 11.65 (s, 1H), 10.32 (s, 1H), 9.09 (s, 1H), 8.54 (d, J=8.4 Hz, 1H), 7.92 (d, J=8.4 Hz, 2H), 7.80 (d, J=8.8 Hz, 2H), 7.66 (d, J=8.4 Hz, 1H), 7.56 (d, J=8.8 Hz, 2H), 7.04 (d, J=8.8 Hz, 2H), 4.59 (s, 2H), 3.81 (s, 3H). [M+H]+: 416.
    • Example 121 4-Methoxy-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00132
  • 1H NMR (400 MHz, DMSO-d6) δ 11.66 (s, 1H), 9.10 (s, 1H), 8.57 (d, J=8.4 Hz, 1H), 7.95 (d, J=8.4 Hz, 2H), 7.70-7.62 (m, 3H), 7.49-7.40 (m, 3H), 7.16 (d, J=8.8 Hz, 2H), 4.60 (s, 2H), 3.87 (s, 3H). [M+H]+: 359.
    • Example 122 4-Fluoro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00133
  • 1H NMR (400 MHz, DMSO-d6) δ 11.73 (s, 1H), 9.13 (s, 1H), 8.55 (d, J=8.4 Hz, 1H), 8.06-8.03 (m, 2H), 7.72 (d, J=8.4 Hz, 1H), 7.63 (d, J=8.4 Hz, 2H), 7.51-7.48 (m, 4H), 7.45-7.40 (m, 1H), 4.61 (s, 2H). [M+H]+: 347.
    • Example 123 N-(7-(4-fluorophenyl)-3-oxoisoindolin-4-yl)-4-methoxy benzamide
  • Figure US20160311772A1-20161027-C00134
  • 1H NMR (400 MHz, DMSO-d6) δ 11.66 (s, 1H), 9.12 (s, 1H), 8.56 (d, J=8.4 Hz, 1H), 7.95 (d, J=8.4 Hz, 2H), 7.70-7.65 (m, 3H), 7.32 (t, J=8.4 Hz, 2H), 7.16 (t, J=8.8 Hz, 2H), 4.59 (s, 2H), 3.87 (m, 3H). [M+H]+: 377.
    • Example 124 4-Acetamido-N-(7-(4-fluorophenyl)-3-oxoisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00135
  • 1H NMR (400 MHz, DMSO-d6) δ 10.82 (s, 1H), 10.39 (s, 1H), 8.78 (s, 1H), 8.06 (d, J=8.4 Hz, 2H), 7.79 (d, J=8.8 Hz, 2H), 7.61 (dd, J=8.6, 5.6 Hz, 2H), 7.56 (d, J=8.4 Hz, 1H), 7.29 (t, J=8.8 Hz, 2H), 7.24 (d, J=8.4 Hz, 1H), 4.54 (s, 2H), 2.10 (s, 3H). [M+H]+: 404.
    • Example 125 N-(3-oxo-7-(thiophen-2-yl)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00136
  • 1H NMR (400 MHz, DMSO-d6) δ 11.74 (br s, 1H), 9.23 (br s, 1H), 8.55 (d, J=8.4 Hz, 1H), 7.98 (d, J=6.8 Hz, 2H), 7.92 (d, J=8.4 Hz, 1H), 7.68-7.61 (m, 4H), 7.49 (d, J=3.2 Hz, 1H), 7.23-7.21 (m, 1H), 4.68 (s, 2H); [M+H]+: 335.
    • Example 126 N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00137
  • 1H NMR (400 MHz, DMSO-d6) δ 11.71 (br s, 1H), 9.20 (br s, 1H), 8.55 (d, J=8.4 Hz, 1H), 8.00-7.97 (m, 3H), 7.84-7.83 (m, 1H), 7.68-7.60 (m, 3H), 6.89 (d, J=3.6 Hz, 1H), 6.68-6.66 (m, 1H), 4.66 (s, 2H); [M+H]+: 319.
    • Example 127 N-(3-oxo-7-(pyridin-4-yl)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00138
  • 1H NMR (400 MHz, DMSO-d6) δ 11.81 (br s, 1H), 9.21 (br s, 1H), 8.67 (d, J=6.0 Hz, 2H), 8.62 (d, J=8.4 Hz, 1H), 8.00 (d, J=6.8 Hz, 2H), 7.88 (d, J=8.4 Hz, 1H), 7.69-7.63 (m, 5H), 4.71 (s, 2H); [M+H]+: 330.
    • Example 128 N-(3-oxo-7-(pyridin-4-yl)isoindolin-4-yl)benzamide hydrochloride
  • Figure US20160311772A1-20161027-C00139
  • 1H NMR (400 MHz, DMSO-d6) δ 11.86 (br s, 1H), 9.26 (br s, 1H), 8.88 (d, J=6.0 Hz, 2H), 8.67 (d, J=8.4 Hz, 1H), 8.10 (d, J=5.6 Hz, 1H), 8.03-7.99 (m, 3H), 7.72-7.62 (m, 3H), 4.76 (s, 2H); [M+H]+: 330 (free form).
    • Example 129 2-Methoxy-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00140
  • 1H NMR (400 MHz, DMSO-d6) δ 12.16 (br s, 1H), 8.85 (br s, 1H), 8.80 (d, J=8.4 Hz, 1H), 8.07 (d, J=6.8 Hz, 1H), 7.67 (d, J=8.8 Hz, 1H), 7.62-7.58 (m, 3H), 7.49 (t, J=7.6 Hz, 2H), 7.40 (t, J=7.2 Hz, 1H), 7.26 (d, J=8.4 Hz, 1H), 7.13 (t, J=7.4 Hz, 1H), 4.55 (s, 2H), 4.07 (s, 3H); [M+H]+: 359.
    • Example 130 3-fluoro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00141
  • 1H NMR (400 MHz, DMSO-d6) δ 11.75 (br s, 1H), 9.11 (br s, 1H), 8.54 (d, J=8.4 Hz, 1H), 7.82 (d, J=7.6 Hz, 1H), 7.74-7.67 (m, 3H), 7.63 (t, J=7.2 Hz, 2H), 7.57-7.47 (m, 3H), 7.40 (t, J=7.4 Hz, 1H), 4.61 (s, 2H); [M+H]+: 347.
    • Example 131 4-(Methylthio)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00142
  • 1H NMR (400 MHz, DMSO-d6) δ 11.70 (br s, 1H), 9.07 (br s, 1H), 8.56 (d, J=8.4 Hz, 1H), 7.91 (d, J=8.4 Hz, 2H), 7.71 (d, J=8.4 Hz, 1H), 7.62 (d, J=7.6 Hz, 2H), 7.51-7.46 (m, 4H), 7.40 (t, J=7.4 Hz, 1H), 4.60 (s, 2H), 2.56 (s, 3H); [M+H]+: 375.
    • Example 132 N-(3-oxo-7-(4-propoxyphenyl)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00143
  • 1H NMR (400 MHz, DMSO-d6) δ 11.72 (br s, 1H), 9.06 (br s, 1H), 8.55 (d, J=8.4 Hz, 1H), 7.99 (d, J=6.8 Hz, 2H), 7.68-7.60 (m, 4H), 7.55-7.50 (m, 2H), 7.03 (d, J=8.8 Hz, 2H), 4.58 (s, 2H), 4.00-3.94 (m, 2H), 1.78-1.71 (m, 2H), 1.00 (t, J=7.2 Hz, 3H); [M+H]+: 387.
    • Example 133 N-(7-(4-isopropylphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00144
  • 1H NMR (400 MHz, DMSO-d6) δ 11.73 (br s, 1H), 9.06 (br s, 1H), 8.56 (d, J=8.0 Hz, 1H), 7.99 (d, J=7.6 Hz, 2H), 7.71-7.60 (m, 4H), 7.55 (d, J=7.6 Hz, 2H), 7.36 (d, J=7.2 Hz, 2H), 4.61 (s, 2H), 1.25 (d, J=6.8 Hz, 6H); [M+H]+: 371.
    • Example 134 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)furan-2-carboxamide
  • Figure US20160311772A1-20161027-C00145
  • 1H NMR (400 MHz, DMSO-d6) δ 9.92 (br s, 1H), 8.48 (d, J=8.4 Hz, 1H), 8.02 (d, J=1.2 Hz, 1H), 7.54 (d, J=8.4 Hz, 1H), 7.31 (d, J=3.2 Hz, 2H), 7.17-7.09 (m, 2H), 6.94 (dd, J=7.4, 1.8 Hz, 1H), 6.77 (dd, J=3.6, 1.6 Hz, 1H), 4.29 (s, 2H), 3.85 (s, 3H), 3.45 (s, 3H); [M+H]+: 379.
    • Example 135 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-fluoro benzamide
  • Figure US20160311772A1-20161027-C00146
  • 1H NMR (400 MHz, DMSO-d6) δ 11.63 (br s, 1H), 8.98 (br s, 1H), 8.50 (d, J=8.4 Hz, 1H), 8.06-8.02 (m, 2H), 7.56 (d, J=8.4 Hz, 1H), 7.47 (t, J=8.8 Hz, 2H), 7.18-7.10 (m, 2H), 6.95 (dd, J=7.4, 1.8 Hz, 1H), 4.31 (s, 2H), 3.86 (s, 3H), 3.45 (s, 3H); [M+H]+: 407.
    • Example 136 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)thiophene-2-carboxamide
  • Figure US20160311772A1-20161027-C00147
  • 1H NMR (400 MHz, DMSO-d6) δ 11.60 (br s, 1H), 8.90 (br s, 1H), 8.40 (d, J=8.4 Hz, 1H), 7.97 (dd, J=5.0, 1.0 Hz, 1H), 7.76 (dd, J=3.6, 0.8 Hz, 1H), 7.54 (d, J=8.4 Hz, 1H), 7.32-7.29 (m, 1H), 7.18-7.10 (m, 2H), 6.95 (dd, J=7.4, 1.8 Hz, 1H), 4.31 (s, 2H), 3.86 (s, 3H), 3.45 (s, 3H); [M+H]+: 395.
    • Example 137 4-Fluoro-2-methyl-N-(3-oxo-7-phenylisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00148
  • 1H NMR (400 MHz, DMSO-d6) δ 11.40 (br s, 1H), 8.91 (br s, 1H), 8.50 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.4 Hz, 2H), 7.50 (d, J=8.4 Hz, 1H), 7.17-7.09 (m, 2H), 6.94 (d, J=6.4 Hz, 1H), 6.67 (d, J=8.4 Hz, 2H), 6.57 (t, J=5.2 Hz, 1H), 4.29 (s, 2H), 3.85 (s, 3H), 3.44 (s, 3H), 3.17-3.11 (m, 2H), 2.35-2.31 (m, 6H), 1.72-1.68 (m, 2H), 1.52-1.48 (m, 4H), 1.39-1.37 (m, 2H); [M+H]+: 529.
    • Example 138 4-Acetamido-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00149
  • 1H NMR (400 MHz, DMSO-d6) δ 11.58 (s, 1H), 10.30 (s, 1H), 8.93 (s, 1H), 8.50 (d, J=8.4 Hz, 1H), 7.92 (d, J=8.5 Hz, 2H), 7.80 (d, J=8.4 Hz, 2H), 7.51 (d, J=8.3 Hz, 1H), 7.41 (s, 1H), 7.32 (d, J=7.6 Hz, 1H), 7.14 (d, J=8.4 Hz, 1H), 7.05 (t, J=7.4 Hz, 1H), 4.27 (s, 2H), 3.77 (s, 3H), 1.24 (s, 3H); [M+H]+: 416.
    • Example 139 4-(Dimethylamino)-N-(3-oxo-7-phenylisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00150
  • 1H NMR (400 MHz, DMSO-d6) δ 11.85 (br s, 1H), 8.57 (s, 1H), 8.48 (s, 1H), 7.84 (d, J=7.6 Hz, 2H), 7.79-7.77 (m, 1H), 7.65 (s, 1H), 7.53-7.48 (m, 3H), 7.19-7.16 (m, 1H), 6.35 (br s, 1H), 4.49-4.40 (m, 2H), 3.91-3.85 (m, 2H), 3.70-3.42 (m, 7H), 2.72-2.63 (m, 3H); [M+H]+: 372.
    • Example 140 4-Acetamido-N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00151
  • 1H NMR (400 MHz, DMSO-d6) δ 11.62 (s, 1H), 10.30 (s, 1H), 9.15 (s, 1H), 8.54 (d, J=8.6 Hz, 1H), 7.94 (dd, J=21.0, 8.6 Hz, 3H), 7.85-7.75 (m, 3H), 6.87 (d, J=3.5 Hz, 1H), 6.66 (dd, J=3.5, 1.8 Hz, 1H), 4.65 (s, 2H), 2.10 (s, 3H); [M+H]+: 376.
    • Example 141 4-Fluoro-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00152
  • 1H NMR (400 MHz, DMSO-d6) δ 11.63 (s, 1H), 8.95 (s, 1H), 8.48 (d, J=8.3 Hz, 1H), 8.09-7.99 (m, 2H), 7.52 (d, J=8.4 Hz, 1H), 7.46 (t, J=8.7 Hz, 2H), 7.43-7.38 (m, 1H), 7.31 (dd, J=7.5, 1.7 Hz, 1H), 7.14 (d, J=8.3 Hz, 1H), 7.05 (t, J=7.4 Hz, 1H), 4.27 (s, 2H), 3.77 (s, 3H); [M+H]+: 377.
    • Example 142 2-Fluoro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00153
  • 1H NMR (400 MHz, DMSO-d6) δ 11.54 (d, J=6.5 Hz, 1H), 8.98 (s, 1H), 8.64 (d, J=8.5 Hz, 1H), 7.97 (t, J=7.8 Hz, 1H), 7.70 (t, J=8.3 Hz, 2H), 7.62 (d, J=7.6 Hz, 2H), 7.50 (t, J=7.7 Hz, 2H), 7.46-7.37 (m, 3H), 4.57 (s, 2H); [M+H]+: 347.
    • Example 143 4-Chloro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00154
  • 1H NMR (400 MHz, DMSO-d6) δ 11.74 (s, 1H), 9.09 (s, 1H), 8.55 (d, J=8.4 Hz, 1H), 7.99 (d, J=8.2 Hz, 2H), 7.72 (dd, J=8.3, 5.5 Hz, 3H), 7.62 (d, J=7.6 Hz, 2H), 7.50 (t, J=7.5 Hz, 2H), 7.41 (t, J=7.4 Hz, 1H), 4.61 (s, 2H); [M+H]+: 363.
    • Example 144 N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00155
  • 1H NMR (400 MHz, DMSO-d6) δ 11.67 (s, 1H), 8.98 (s, 1H), 8.52 (d, J=8.4 Hz, 1H), 8.02-7.95 (m, 2H), 7.65 (dt, J=14.4, 6.9 Hz, 3H), 7.53 (d, J=8.4 Hz, 1H), 7.46-7.38 (m, 1H), 7.32 (dd, J=7.4, 1.7 Hz, 1H), 7.15 (d, J=8.2 Hz, 1H), 7.05 (dd, J=7.9, 6.8 Hz, 1H), 4.28 (s, 2H), 3.77 (s, 3H); [M+H]+: 359.
    • Example 145 N-(7-(3-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00156
  • 1H NMR (400 MHz, DMSO-d6) δ 11.75 (s, 1H), 9.11 (s, 1H), 8.57 (d, J=8.4 Hz, 1H), 7.99 (dt, J=6.8, 1.5 Hz, 2H), 7.74 (d, J=8.5 Hz, 1H), 7.65 (ddd, J=14.3, 7.8, 6.1 Hz, 3H), 7.40 (t, J=7.9 Hz, 1H), 7.18 (d, J=8.0 Hz, 1H), 7.15 (t, J=2.1 Hz, 1H), 6.97 (dd, J=7.7, 2.4 Hz, 1H), 4.61 (s, 2H), 3.82 (s, 3H); [M+H]+: 359.
    • Example 146 N-(3-oxo-7-(thiophen-3-yl)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00157
  • 1H NMR (400 MHz, DMSO-d6) δ 11.74 (s, 1H), 9.19 (s, 1H), 8.54 (d, J=8.5 Hz, 1H), 7.98 (d, J=7.4 Hz, 2H), 7.91 (d, J=8.5 Hz, 1H), 7.84 (d, J=2.5 Hz, 1H), 7.75-7.55 (m, 5H), 4.68 (s, 2H); [M+H]+: 335.
    • Example 147 N-(7-(3-cyanophenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00158
  • 1H NMR (400 MHz, DMSO-d6) δ 11.77 (s, 1H), 9.17 (s, 1H), 8.60 (d, J=8.4 Hz, 1H), 8.13 (s, 1H), 8.03-7.94 (m, 3H), 7.88 (d, J=7.8 Hz, 1H), 7.80 (d, J=8.4 Hz, 1H), 7.74-7.60 (m, 4H), 4.66 (s, 2H); [M+H]+: 354.
    • Example 148 N-(7-(3-(dimethylamino)phenyl)-3-oxoisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00159
  • 1H NMR (400 MHz, DMSO-d6) δ 11.74 (s, 1H), 9.08 (s, 1H), 8.56 (d, J=8.4 Hz, 1H), 8.02-7.95 (m, 2H), 7.75-7.58 (m, 4H), 7.28 (t, J=8.0 Hz, 1H), 6.90-6.83 (m, 2H), 6.79-6.72 (m, 1H), 4.59 (s, 2H), 2.95 (s, 6H); [M+H]+: 372.
    • Example 149 N-(7-(2-fluorophenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00160
  • 1H NMR (400 MHz, DMSO-d6) δ 11.71 (s, 1H), 9.08 (s, 1H), 8.58 (d, J=8.4 Hz, 1H), 7.99 (dt, J=6.9, 1.5 Hz, 2H), 7.72-7.55 (m, 5H), 7.54-7.44 (m, 1H), 7.42-7.28 (m, 2H), 4.40 (s, 2H); [M+H]+: 347.
    • Example 150 N-(7-(furan-3-yl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00161
  • 1H NMR (400 MHz, DMSO-d6) δ 11.68 (s, 1H), 9.18 (s, 1H), 8.52 (d, J=8.5 Hz, 1H), 8.11 (s, 1H), 8.01-7.94 (m, 2H), 7.87 (d, J=8.5 Hz, 1H), 7.82 (t, J=1.7 Hz, 1H), 7.72-7.57 (m, 3H), 7.05 (d, J=1.8 Hz, 1H), 4.59 (s, 2H); [M+H]+: 319.
    • Example 151 N-(7-(3-fluorophenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00162
  • 1H NMR (400 MHz, DMSO-d6) δ 11.76 (s, 1H), 9.14 (s, 1H), 8.59 (d, J=8.4 Hz, 1H), 7.99 (d, J=7.4 Hz, 2H), 7.76 (d, J=8.4 Hz, 1H), 7.69-7.59 (m, 3H), 7.50 (d, J=11.8 Hz, 3H), 7.24 (s, 1H), 4.64 (s, 2H); [M+H]+: 347.
    • Example 152 N-(3-oxo-7-(pyridin-3-yl)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00163
  • 1H NMR (400 MHz, DMSO-d6) δ 11.73 (s, 1H), 9.06 (s, 1H), 8.84 (d, J=2.4 Hz, 1H), 8.61 (d, J=7.1 Hz, 2H), 8.03 (dd, J=22.0, 7.5 Hz, 3H), 7.78 (d, J=8.4 Hz, 1H), 7.64 (dt, J=14.6, 7.2 Hz, 3H), 7.52 (dd, J=8.0, 4.8 Hz, 1H), 4.64 (s, 2H); [M+H]+: 330.
    • Example 153 N-(3-oxo-7-(pyridin-3-yl)isoindolin-4-yl)benzamide hydrochloride
  • Figure US20160311772A1-20161027-C00164
  • 1H NMR (400 MHz, DMSO-d6) δ 11.77 (s, 1H), 9.18 (s, 1H), 9.04 (s, 1H), 8.79 (d, J=5.2 Hz, 1H), 8.64 (d, J=8.4 Hz, 1H), 8.49 (d, J=8.0 Hz, 1H), 8.00 (d, J=7.2 Hz, 2H), 7.90-7.86 (m, 2H), 7.69-7.62 (m, 3H), 4.68 (s, 2H); [M+H]+: 330.
    • Example 154 N-(3-oxo-7-(pyrimidin-5-yl)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00165
  • 1H NMR (400 MHz, DMSO-d6) δ 11.75 (s, 1H), 9.22 (s, 1H), 9.10 (s, 3H), 8.63 (d, J=8.3 Hz, 1H), 8.00 (d, J=7.4 Hz, 2H), 7.87 (d, J=8.5 Hz, 1H), 7.64 (s, 3H), 4.70 (s, 2H); [M+H]+: 331.
    • Example 155 3-Chloro-N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide
  • Figure US20160311772A1-20161027-C00166
  • 1H NMR (400 MHz, DMSO-d6) δ 11.56 (s, 1H), 8.98 (s, 1H), 8.48 (d, J=8.5 Hz, 1H), 8.03 (d, J=5.3 Hz, 1H), 7.70 (d, J=8.4 Hz, 1H), 7.62 (t, J=7.2 Hz, 2H), 7.49 (t, J=7.5 Hz, 2H), 7.41 (t, J=7.3 Hz, 1H), 7.28 (d, J=5.3 Hz, 1H), 4.58 (s, 2H); [M+H]+: 369.
    • Example 156 5-Bromo-N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide
  • Figure US20160311772A1-20161027-C00167
  • 1H NMR (400 MHz, DMSO-d6) δ 11.63 (s, 1H), 9.14 (s, 1H), 8.39 (d, J=8.4 Hz, 1H), 7.71 (d, J=8.4 Hz, 1H), 7.62 (d, J=7.3 Hz, 2H), 7.56 (d, J=4.4 Hz, 1H), 7.51-7.45 (m, 3H), 7.40 (t, J=7.3 Hz, 1H), 4.60 (s, 2H); [M+H]+: 413.
    • Example 157 3-Bromo-N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide
  • Figure US20160311772A1-20161027-C00168
  • 1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 9.01 (s, 1H), 8.49 (d, J=8.4 Hz, 1H), 7.99 (d, J=5.2 Hz, 1H), 7.71 (d, J=8.4 Hz, 1H), 7.62 (d, J=7.4 Hz, 2H), 7.50 (t, J=7.6 Hz, 2H), 7.41 (t, J=7.2 Hz, 1H), 7.32 (d, J=5.2 Hz, 1H), 4.58 (s, 2H); [M+H]+: 413.
    • Example 158 4-Fluoro-N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00169
  • 1H NMR (400 MHz, DMSO-d6) δ 11.68 (s, 1H), 9.19 (s, 1H), 8.52 (d, J=8.6 Hz, 1H), 8.03 (dd, J=8.8, 5.4 Hz, 2H), 7.88 (d, J=8.5 Hz, 1H), 7.83 (d, J=1.4 Hz, 1H), 7.47 (t, J=8.8 Hz, 2H), 6.88 (d, J=3.4 Hz, 1H), 6.67 (dd, J=3.4, 1.8 Hz, 1H), 4.66 (s, 2H); [M+H]+: 337.
    • Example 159 N-(3-oxo-7-phenylisoindolin-4-yl)pentanamide
  • Figure US20160311772A1-20161027-C00170
  • 1H NMR (400 MHz, DMSO-d6) δ 10.66 (s, 1H), 8.98 (s, 1H), 8.42 (d, J=8.5 Hz, 1H), 7.63 (d, J=8.5 Hz, 1H), 7.59 (d, J=7.3 Hz, 2H), 7.48 (t, J=7.6 Hz, 2H), 7.39 (t, J=7.2 Hz, 1H), 4.55 (s, 2H), 2.42 (t, J=7.5 Hz, 2H), 1.63 (quint, J=7.3 Hz, 2H), 1.37 (quint, J=7.4 Hz, 2H), 0.91 (t, J=7.4 Hz, 3H); [M+H]+: 309.
    • Example 160 N-(3-oxo-7-phenylisoindolin-4-yl)acetamide
  • Figure US20160311772A1-20161027-C00171
  • 1H NMR (400 MHz, DMSO-d6) δ 10.60 (s, 1H), 8.99 (s, 1H), 8.40 (d, J=8.4 Hz, 1H), 7.63 (d, J=8.4 Hz, 1H), 7.59 (d, J=7.1 Hz, 2H), 7.48 (t, J=7.5 Hz, 2H), 7.39 (t, J=7.3 Hz, 1H), 4.55 (s, 2H), 2.17 (s, 3H); [M+H]+: 267.
    • Example 161 N-(7-(2-chloropyrimidin-4-yl)-3-oxoisoindolin-4-yl)acetamide
  • Figure US20160311772A1-20161027-C00172
  • 1H NMR (400 MHz, DMSO-d6) δ 10.81 (s, 1H), 9.11 (s, 1H), 8.82 (d, J=5.2 Hz, 1H), 8.46 (d, J=8.8 Hz, 1H), 8.36 (d, J=8.8 Hz, 2H), 8.12 (d, J=5.6 Hz, 1H), 4.78 (s, 2H), 2.20 (s, 3H). [M+H]+: 303.
    • Example 162 N-(7-(2-((3-methoxyphenyl)amino)pyrimidin-4-yl)-3-oxoisoindolin-4-yl)acetamide
  • Figure US20160311772A1-20161027-C00173
  • 1H NMR (400 MHz, DMSO-d6) δ 10.78 (s, 1H), 9.55 (s, 1H), 9.14 (s, 1H), 8.56 (d, J=5.6 Hz, 1H), 8.44 (d, J=8.4 Hz, 1H), 8.22 (d, J=8.8 Hz, 1H), 7.43-7.44 (m, 1H), 7.35 (d, J=5.2 Hz, 1H), 7.33 (d, J=8.4 Hz, 1H), 7.21 (t, J=8.2 Hz, 1H), 6.56 (dd, J=8.2, 2.2 Hz, 1H), 4.84 (s, 2H), 3.74 (s, 3H), 2.19 (s, 3H). [M+H]+: 390.
    • Example 163 N-(7-(2-((3-fluorophenyl)amino)pyrimidin-4-yl)-3-oxoisoindolin-4-yl) acetamide
  • Figure US20160311772A1-20161027-C00174
  • 1H NMR (400 MHz, DMSO-d6) δ 10.78 (s, 1H), 9.79 (s, 1H), 9.16 (s, 1H), 8.60 (d, J=5.2 Hz, 1H), 8.45 (d, J=8.8 Hz, 1H), 8.24 (d, J=8.8 Hz, 1H), 7.78 (d, J=11.6 Hz, 1H), 7.50 (d, J=8.0 Hz, 1H), 7.42 (d, J=5.6 Hz, 1H), 7.36-7.30 (m, 1H), 6.78 (t, J=8.0 Hz, 1H), 4.85 (s, 2H), 2.19 (s, 3H). [M+H]+: 378.
    • Example 164 N-(3-oxo-7-(2-(m-tolylamino)pyrimidin-4-yl)isoindolin-4-yl) acetamide
  • Figure US20160311772A1-20161027-C00175
  • 1H NMR (400 MHz, DMSO-d6) δ 10.78 (s, 1H), 9.49 (s, 1H), 9.14 (s, 1H), 8.54 (d, J=5.2 Hz, 1H), 8.44 (d, J=8.8 Hz, 1H), 8.22 (d, J=8.8 Hz, 1H), 7.55 (s, 1H), 7.51 (d, J=8.4 Hz, 1H), 7.34 (d, J=5.2 Hz, 1H), 7.19 (t, J=8.0 Hz, 1H), 6.81 (d, J=8.0 Hz, 1H), 4.82 (s, 2H), 2.30 (s, 3H), 2.19 (s, 3H). [M+H]+: 374.
    • Example 165 N-(3-oxo-7-(2-(p-tolylamino)pyrimidin-4-yl)isoindolin-4-yl) acetamide
  • Figure US20160311772A1-20161027-C00176
  • 1H NMR (400 MHz, DMSO-d6) δ 10.78 (s, 1H), 9.46 (s, 1H), 9.12 (s, 1H), 8.52 (d, J=5.2 Hz, 1H), 8.44 (d, J=8.8 Hz, 1H), 8.21 (d, J=8.8 Hz, 1H), 7.59 (d, J=8.4 Hz, 2H), 7.32 (d, J=5.2 Hz, 1H), 7.12 (d, J=8.4 Hz, 2H), 4.80 (s, 2H), 2.27 (s, 3H), 2.19 (s, 3H). [M+H]+: 374.
    • Example 166 N-(7-(2-((3-methoxyphenyl)amino)pyrimidin-4-yl)-3-oxoisoindolin-4-yl)propionamide
  • Figure US20160311772A1-20161027-C00177
  • 1H NMR (400 MHz, DMSO-d6) δ 10.84 (s, 1H), 9.56 (s, 1H), 9.14 (s, 1H), 8.55 (d, J=5.6 Hz, 1H), 8.46 (d, J=8.4 Hz, 1H), 8.23 (d, J=8.4 Hz, 1H), 7.44 (s, 1H), 7.36 (d, J=5.2 Hz, 1H), 7.33 (d, J=8.4 Hz, 1H), 7.21 (t, J=8.0 Hz, 2H), 6.56 (dd, J=8.2, 2.2 Hz, 1H), 4.84 (s, 2H), 3.74 (s, 3H), 2.49-2.46 (m, 2H), 1.15 (t, J=7.4 Hz, 3H). [M+H]+: 404.
    • Example 167 N-(7-(4-(methylsulfonyl)phenyl)-3-oxoisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00178
  • 1H NMR (400 MHz, DMSO-d6) δ 11.78 (s, 1H), 9.14 (s, 1H), 8.62 (d, J=8.4 Hz, 1H), 8.05-7.99 (m, 5H), 7.91 (d, J=8.3 Hz, 2H), 7.81 (d, J=8.5 Hz, 1H), 7.69-7.61 (m, 3H), 4.66 (s, 2H), 3.28 (s, 3H); [M+H]+: 407.
    • Example 168 N-(7-(3-(methylsulfonyl)phenyl)-3-oxoisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00179
  • 1H NMR (400 MHz, DMSO-d6) δ 11.77 (s, 1H), 9.13 (s, 1H), 8.63 (d, J=8.4 Hz, 1H), 8.11 (s, 1H), 8.02-8.01 (m, 3H), 7.98 (d, J=11.0 Hz, 1H), 7.84 (d, J=8.5 Hz, 1H), 7.78 (t, J=7.8 Hz, 1H), 7.71-7.62 (m, 3H), 4.64 (s, 2H), 3.31 (s, 3H); [M+H]+: 407.
    • Example 169 N-(7-(3-acetamidophenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00180
  • 1H NMR (400 MHz, DMSO-d6) δ 11.74 (s, 1H), 10.04 (s, 1H), 9.10 (s, 1H), 8.59 (d, J=8.4 Hz, 1H), 7.99 (d, J=7.2 Hz, 2H), 7.83 (s, 1H), 7.71-7.58 (m, 5H), 7.41 (t, J=7.8 Hz, 1H), 7.30 (d, J=7.2 Hz, 1H), 4.58 (s, 2H), 2.07 (s, 3H); [M+H]+: 386.
    • Example 170 5-Chloro-N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide
  • Figure US20160311772A1-20161027-C00181
  • 1H NMR (400 MHz, DMSO-d6) δ 11.64 (s, 1H), 9.14 (s, 1H), 8.39 (d, J=8.4 Hz, 1H), 7.71 (d, J=8.4 Hz, 1H), 7.63-7.61 (m, 2H), 7.49 (t, J=7.5 Hz, 3H), 7.41 (d, J=7.2 Hz, 2H), 7.36 (d, J=4.0 Hz, 1H), 4.61 (s, 2H); [M+H]+: 369
    • Example 171 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00182
  • 1H NMR (400 MHz, DMSO-d6) δ 11.66 (s, 1H), 8.95 (s, 1H), 8.53 (d, J=8.4 Hz, 1H), 7.99 (d, J=7.1 Hz, 2H), 7.69-7.60 (m, 3H), 7.56 (d, J=8.3 Hz, 1H), 7.18-7.11 (m, 2H), 6.95 (d, J=7.5 Hz, 1H), 4.31 (s, 2H), 3.86 (s, 3H), 3.46 (s, 3H); [M+H]+: 389.
    • Example 172 N-(7-(3,5-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00183
  • 1H NMR (400 MHz, DMSO-d6) δ 11.74 (s, 1H), 9.07 (s, 1H), 8.56 (d, J=8.4 Hz, 1H), 7.99 (d, J=7.1 Hz, 1H), 7.73 (d, J=8.5 Hz, 2H), 7.68-7.61 (m, 3H), 6.73 (d, J=2.2 Hz, 2H), 6.54 (s, 1H), 4.61 (s, 2H), 3.81 (s, 6H); [M+H]+: 389.
    • Example 173 N-(7-cyclopropyl-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00184
  • 1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 8.95 (s, 1H), 8.36 (d, J=8.4 Hz, 1H), 7.95 (d, J=7.4 Hz, 2H), 7.66-7.58 (m, 4H), 7.17 (d, J=8.2 Hz, 1H), 4.50 (s, 2H), 1.89 (m, 1H), 0.96 (d, J=7.0 Hz, 2H), 0.75 (d, J=5.6 Hz, 2H); [M+H]+: 293.
    • Example 174 N-(7-(2-chlorophenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00185
  • 1H NMR (400 MHz, DMSO-d6) δ 11.63 (s, 1H), 9.01 (s, 1H), 8.56 (d, J=8.9 Hz, 1H), 7.99 (d, J=6.9 Hz, 2H), 7.69-7.61 (m, 3H), 7.56-7.45 (m, 4H), 4.29 (s, 2H); [M+H]+: 363.
    • Example 175 N-(7-(2,4-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00186
  • 1H NMR (400 MHz, DMSO-d6) δ 11.64 (s, 1H), 8.92 (s, 1H), 8.49 (d, J=8.5 Hz, 1H), 7.99 (d, J=7.4 Hz, 2H), 7.69-7.60 (m, 3H), 7.48 (d, J=8.4 Hz, 1H), 7.23 (d, J=8.4 Hz, 1H), 6.69 (d, J=2.1 Hz, 1H), 6.63 (d, J=8.0 Hz, 1H), 4.26 (s, 2H), 3.82 (s, 3H), 3.76 (s, 3H); [M+H]+: 389.
    • Example 176 N-(7-(3,4-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00187
  • 1H NMR (400 MHz, DMSO-d6) δ 11.73 (s, 1H), 9.06 (s, 1H), 8.56 (d, J=8.6 Hz, 1H), 7.99 (d, J=7.0 Hz, 2H), 7.71 (d, J=8.5 Hz, 1H), 7.68-7.61 (m, 3H), 7.17 (s, 1H), 7.14 (d, J=8.1 Hz, 1H), 7.05 (d, J=8.2 Hz, 1H), 4.61 (s, 2H), 3.83 (s, 3H), 3.81 (s, 3H); [M+H]+: 389.
    • Example 177 N-(7-(3-ethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00188
  • 1H NMR (400 MHz, DMSO-d6) δ 11.74 (s, 1H), 9.06 (s, 1H), 8.57 (d, J=8.6 Hz, 1H), 7.99 (d, J=7.2 Hz, 2H), 7.73 (d, J=8.4 Hz, 1H), 7.68-7.61 (m, 3H), 7.39 (t, J=7.9 Hz, 1H), 7.16 (d, J=7.7 Hz, 1H), 6.97 (s, 1H), 6.96 (d, J=6.0 Hz, 1H), 4.60 (s, 2H), 4.10 (q, J=6.9 Hz, 2H), 1.36 (t, J=6.9 Hz, 3H); [M+H]+: 373.
    • Example 178 N-(7-(2,5-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00189
  • 1H NMR (400 MHz, DMSO-d6) δ 11.65 (s, 1H), 8.94 (s, 1H), 8.51 (d, J=8.3 Hz, 1H), 7.99 (d, J=7.1 Hz, 2H), 7.68-7.61 (m, 3H), 7.54 (d, J=8.4 Hz, 1H), 7.07 (d, J=9.0. Hz, 1H), 6.97 (dd, J=8.9, 3.0 Hz, 1H), 6.90 (d, J=3.0 Hz, 1H), 4.29 (s, 2H), 3.75 (s, 3H), 3.70 (s, 3H); [M+H]+: 389.
    • Example 179 N-(7-(4-chlorophenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00190
  • 1H NMR (400 MHz, DMSO-d6) δ 11.74 (s, 1H), 9.10 (s, 1H), 8.58 (d, J=8.3 Hz, 1H), 7.99 (d, J=7.2 Hz, 2H), 7.73 (d, J=8.3 Hz, 1H), 7.68-7.63 (m, 5H), 7.54 (d, J=8.4 Hz, 1H), 4.60 (s, 2H); [M+H]+: 363.
    • Example 180 N-(7-(3-chlorophenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00191
  • 1H NMR (400 MHz, DMSO-d6) δ 11.75 (s, 1H), 9.10 (s, 1H), 8.58 (d, J=8.4 Hz, 1H), 7.99 (d, J=7.1 Hz, 2H), 7.75 (d, J=8.4 Hz, 1H), 7.69-7.59 (m, 5H), 7.54-7.46 (m, 2H), 4.62 (s, 2H); [M+H]+: 363.
    • Example 181 N-(7-(4-ethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00192
  • 1H NMR (400 MHz, DMSO-d6) δ 11.72 (s, 1H), 9.06 (s, 1H), 8.55 (d, J=8.6 Hz, 1H), 7.99 (d, J=7.2 Hz, 2H), 7.68-7.62 (m, 3H), 7.54 (d, J=8.6 Hz, 2H), 7.02 (d, J=8.5 Hz, 2H), 4.58 (s, 2H), 4.09 (q, J=7.1 Hz, 2H), 1.36 (q, J=7.1 Hz, 3H); [M+H]+: 373.
    • Example 182 N-(7-(2-ethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00193
  • 1H NMR (400 MHz, DMSO-d6) δ 11.66 (s, 1H), 8.93 (s, 1H), 8.52 (d, J=8.4 Hz, 1H), 7.99 (d, J=7.0 Hz, 2H), 7.68-7.61 (m, 3H), 7.55 (d, J=8.4 Hz, 1H), 7.38 (t, J=7.8 Hz, 1H), 7.33 (d, J=7.4 Hz, 1H), 7.13 (d, J=8.2 Hz, 1H), 7.04 (d, J=7.3 Hz, 1H), 4.32 (s, 2H), 4.06 (q, J=6.9 Hz, 2H), 1.21 (q, J=7.0 Hz, 3H); [M+H]+: 373.
    • Example 183 N-(7-(2-cyanophenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00194
  • 1H NMR (400 MHz, DMSO-d6) δ 11.69 (s, 1H), 9.09 (s, 1H), 8.61 (d, J=8.6 Hz, 1H), 8.00 (d, J=7.6 Hz, 2H), 7.82-7.76 (m, 2H), 7.72-7.62 (m, 6H), 4.44 (s, 2H); [M+H]+: 354.
    • Example 184 N-(7-(4-butoxyphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00195
  • 1H NMR (400 MHz, DMSO-d6) δ 11.72 (s, 1H), 9.06 (s, 1H), 8.55 (d, J=8.3 Hz, 1H), 7.99 (d, J=7.0 Hz, 2H), 7.68-7.61 (m, 4H), 7.54 (d, J=8.6 Hz, 2H), 7.03 (d, J=8.6 Hz, 2H), 4.58 (s, 2H), 4.03 (t, J=6.4 Hz, 2H), 1.73 (quint, 2H), 1.45 (quint, 2H), 0.95 (t, J=7.4 Hz, 3H); [M+H]+: 401.
    • Example 185 N-(7-(2-(dimethylamino)phenyl)-3-oxoisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00196
  • 1H NMR (400 MHz, DMSO-d6) δ 11.65 (s, 1H), 8.92 (s, 1H), 8.55 (d, J=8.3 Hz, 1H), 7.99 (d, J=7.0 Hz, 2H), 7.70-7.59 (m, 4H), 7.33 (t, J=7.7 Hz, 1H), 7.23 (d, J=7.5 Hz, 1H), 7.12 (d, J=8.2 Hz, 1H), 7.02 (t, J=7.4 Hz, 1H), 4.29 (s, 2H); [M+H]+: 372.
    • Example 186 N-(3-oxo-7-(4-(trifluoromethoxy)phenyl)isoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00197
  • 1H NMR (400 MHz, DMSO-d6) δ 11.75 (s, 1H), 9.12 (s, 1H), 8.59 (d, J=8.4 Hz, 1H), 7.99 (d, J=7.2 Hz, 2H), 7.76 (t, J=7.8 Hz, 3H), 7.70-7.61 (m, 3H), 7.48 (d, J=8.4 Hz, 2H), 4.62 (s, 2H); [M+H]+: 413.
    • Example 187 N-(7-(2,6-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00198
  • 1H NMR (400 MHz, DMSO-d6) δ 11.56 (s, 1H), 8.85 (s, 1H), 8.46 (d, J=8.4 Hz, 1H), 7.99 (d, J=6.9 Hz, 2H), 7.68-7.61 (m, 3H), 7.41-7.7.35 (m, 2H), 6.78 (d, J=8.4 Hz, 2H), 4.08 (s, 2H), 3.69 (s, 6H); [M+H]+: 389.
    • Example 188 N-(3-oxo-7-(4-propylphenyl)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00199
  • 1H NMR (400 MHz, DMSO-d6) δ 11.74 (s, 1H), 9.07 (s, 1H), 8.57 (d, J=8.3 Hz, 1H), 7.99 (d, J=7.1 Hz, 2H), 7.72-7.61 (m, 4H), 7.53 (d, J=8.1 Hz, 2H), 7.31 (d, J=8.0 Hz, 2H), 4.60 (s, 2H), 2.61 (t, J=7.7 Hz, 2H), 1.64 (q, J=7.4 Hz, 2H), 0.94 (t, J=7.3 Hz, 3H); [M+H]+: 371.
    • Example 189 N-(7-(2,3-dihydroxyphenyl)-3-oxoisoindolin-4-yl)-4-fluorobenzamide
  • Figure US20160311772A1-20161027-C00200
  • 1H NMR (400 MHz, DMSO-d6) δ 11.65 (s, 1H), 9.61 (s, 1H), 8.96 (s, 1H), 8.58 (s, 1H), 8.47 (d, J=8.4 Hz, 1H), 8.04 (dd, J=8.8, 5.2 Hz, 2H), 7.53 (d, J=8.4 Hz, 1H), 7.47 (t, J=8.8 Hz, 2H), 6.83 (dd, J=6.4, 3.2 Hz, 1H), 6.74-6.69 (m, 2H), 4.34 (s, 2H); [M+H]+: 379.
    • Example 190 4-Fluoro-N-(7-(2-hydroxy-3-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00201
  • 1H NMR (400 MHz, DMSO-d6) δ 11.65 (s, 1H), 8.98 (s, 1H), 8.88 (s, 1H), 8.48 (d, J=8.4 Hz, 1H), 8.04 (dd, J=8.8, 5.6 Hz, 2H), 7.53 (d, J=8.4 Hz, 1H), 7.47 (t, J=8.8 Hz, 2H), 7.01 (dd, J=5.6, 4.0 Hz, 1H), 6.87-6.85 (m, 2H), 4.34 (s, 2H), 3.85 (s, 3H). [M+H]+: 393.
    • Example 191 4-Fluoro-N-(3-oxo-7-(thiophen-2-yl)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00202
  • 1H NMR (400 MHz, DMSO-d6) δ 11.71 (s, 1H), 9.23 (s, 1H), 8.51 (d, J=8.4 Hz, 1H), 8.05-8.01 (m, 2H), 7.91 (d, J=8.4 Hz, 1H), 7.66 (d, J=5.2 Hz, 1H), 7.49-7.44 (m, 3H), 7.21 (t, J=4.2 Hz, 1H), 4.67 (s, 2H). [M+H]+: 353.
    • Example 192 5-Methyl-N-(3-oxo-7-phenylisoindolin-4-yl)furan-2-carboxamide
  • Figure US20160311772A1-20161027-C00203
  • 1H NMR (400 MHz, DMSO-d6) δ 11.51 (s, 1H), 9.00 (s, 1H), 8.51 (d, J=8.8 Hz, 1H), 7.68 (d, J=8.4 Hz, 2H), 7.62-7.60 (m, 2H), 7.49 (d, J=7.6 Hz, 2H), 7.41-7.38 (m, 1H), 7.20 (d, J=3.2 Hz, 1H), 6.41 (dd, J=3.4, 1.0 Hz, 1H), 4.58 (s, 2H), 2.41 (s, 3H). [M+H]+: 333.
    • Example 193 N-(7-(benzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)-4-fluorobenzamide
  • Figure US20160311772A1-20161027-C00204
  • 1H NMR (400 MHz, DMSO-d6) δ 11.76 (s, 1H), 9.17 (s, 1H), 8.82 (s, 1H), 8.61 (d, J=8.4 Hz, 1H), 8.06 (dd, J=8.6, 5.4 Hz, 2H), 7.92 (d, J=8.4 Hz, 1H), 7.86 (d, J=7.6 Hz, 1H), 7.67 (d, J=7.2 Hz, 1H), 7.54-7.46 (m, 3H), 4.56 (s, 2H). [M+H]+: 388.
    • Example 194 4-Fluoro-N-(7-(2-methylbenzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00205
  • 1H NMR (400 MHz, DMSO-d6) δ 11.75 (s, 1H), 9.15 (s, 1H), 8.60 (d, J=8.8 Hz, 1H), 8.06 (dd, J=8.6, 5.4 Hz, 2H), 7.87 (d, J=8.4 Hz, 1H), 7.70 (d, J=7.2 Hz, 1H), 7.56-7.42 (m, 4H), 4.54 (s, 2H), 2.63 (s, 3H). [M+H]+: 402.
    • Example 195 N-(3-oxo-7-(5-(pyrrolidin-1-ylmethyl)thiophen-2-yl)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00206
  • 1H NMR (400 MHz, DMSO-d6) δ 11.73 (s, 1H), 9.17 (s, 1H), 8.53 (d, J=8.4 Hz, 1H), 7.98 (d, J=7.2 Hz, 2H), 7.86 (d, J=8.4 Hz, 1H), 7.67-7.60 (m, 3H), 7.28 (d, J=3.6 Hz, 1H), 7.01 (d, J=3.2 Hz, 1H), 4.65 (s, 2H), 3.80 (s, 2H), 2.58-2.50 (m, 4H), 1.74-1.70 (m, 4H). [M+H]+: 418.
    • Example 196 N-(3-oxo-7-(5-(piperidin-1-ylmethyl)thiophen-2-yl)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00207
  • 1H NMR (400 MHz, DMSO-d6) δ 11.73 (s, 1H), 9.17 (s, 1H), 8.53 (d, J=8.4 Hz, 1H), 7.98 (d, J=6.8 Hz, 2H), 7.86 (d, J=8.4 Hz, 1H), 7.67-7.60 (m, 3H), 7.28 (d, J=3.6 Hz, 1H), 7.01 (d, J=3.6 Hz, 1H), 4.65 (s, 2H), 3.66 (s, 2H), 2.42-2.38 (m, 4H), 1.54-1.48 (m, 4H), 1.40-1.36 (m, 2H). [M+H]+: 432.
    • Example 197 N-(7-(5-(morpholinomethyl)thiophen-2-yl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00208
  • 1H NMR (400 MHz, DMSO-d6) δ 11.73 (s, 1H), 9.17 (s, 1H), 8.53 (d, J=8.8 Hz, 1H), 7.98 (d, J=6.8 Hz, 2H), 7.86 (d, J=8.4 Hz, 1H), 7.67-7.62 (m, 3H), 7.29 (d, J=3.6 Hz, 1H), 7.04 (d, J=3.6 Hz, 1H), 4.65 (s, 2H), 3.71 (s, 2H), 3.62-3.56 (m, 4H), 2.48-2.42 (m, 4H). [M+H]+: 434.
    • Example 198 tert-Butyl 4-((5-(7-benzamido-1-oxoisoindolin-4-yl)thiophen-2-yl) methyl)piperazine-1-carboxylate
  • Figure US20160311772A1-20161027-C00209
  • 1H NMR (400 MHz, DMSO-d6) δ 11.73 (s, 1H), 9.17 (s, 1H), 8.53 (d, J=8.4 Hz, 1H), 7.98 (d, J=6.8 Hz, 2H), 7.86 (d, J=8.4 Hz, 1H), 7.67-7.62 (m, 3H), 7.30 (d, J=3.6 Hz, 1H), 7.04 (d, J=3.6 Hz, 1H), 4.66 (s, 2H), 3.73 (s, 2H), 3.35-3.30 (m, 4H), 2.42-2.38 (m, 4H), 1.39 (s, 9H). [M+H]+: 533.
    • Example 199 N-(7-(6-fluoropyridin-3-yl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00210
  • 1H NMR (400 MHz, DMSO-d6) δ 11.74 (s, 1H), 9.13 (s, 1H), 8.60 (d, J=8.0 Hz, 1H), 8.51 (s, 1H), 8.28-8.24 (m, 1H), 7.99 (d, J=6.4 Hz, 2H), 7.77 (d, J=8.4 Hz, 1H), 7.67-7.63 (m, 3H), 7.32 (d, J=6.8 Hz, 1H), 4.63 (s, 2H). [M+H]+: 348.
    • Example 200 N-(7-(6-methoxypyridin-3-yl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00211
  • 1H NMR (400 MHz, DMSO-d6) δ 11.72 (s, 1H), 9.09 (s, 1H), 8.57 (d, J=8.4 Hz, 1H), 8.43 (s, 1H), 7.99 (d, J=7.6 Hz, 3H), 7.73-7.62 (m, 3H), 6.94 (d, J=8.0 Hz, 1H), 4.61 (s, 2H), 3.91 (s, 3H). [M+H]+: 360.
    • Example 201 2-Chloro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00212
  • 1H NMR (400 MHz, DMSO-d6) δ 11.12 (s, 1H), 9.02 (s, 1H), 8.54 (d, J=8.4 Hz, 1H), 7.74 (t, J=6.8 Hz, 2H), 7.65-7.59 (m, 4H), 7.57-7.48 (m, 3H), 7.43-7.39 (m, 1H), 4.58 (s, 2H). [M+H]+: 363.
    • Example 202 3-Methoxy-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00213
  • 1H NMR (400 MHz, DMSO-d6) δ 11.73 (s, 1H), 9.08 (s, 1H), 8.56 (d, J=8.4 Hz, 1H), 7.72 (d, J=8.4 Hz, 1H), 7.62 (d, J=7.6 Hz, 2H), 7.55-7.49 (m, 5H), 7.47-7.41 (m, 1H), 7.26-7.23 (m, 1H), 4.60 (s, 2H), 3.87 (s, 3H). [M+H]+: 359.
    • Example 203 N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide
  • Figure US20160311772A1-20161027-C00214
  • 1H NMR (400 MHz, DMSO-d6) δ 11.64 (s, 1H), 9.09 (s, 1H), 8.44 (d, J=8.4 Hz, 1H), 7.97 (d, J=4.8 Hz, 1H), 7.76 (d, J=3.6 Hz, 1H), 7.70 (d, J=8.4 Hz, 1H), 7.62 (d, J=7.6 Hz, 2H), 7.49 (t, J=7.6 Hz, 2H), 7.40 (d, J=7.2 Hz, 1H), 7.31 (d, J=4.2 Hz, 1H), 4.60 (s, 2H). [M+H]+: 335.
    • Example 204 N-(7-(4-acetylphenyl)-3-oxoisoindolin-4-yl)-4-methoxy benzamide
  • Figure US20160311772A1-20161027-C00215
  • 1H NMR (400 MHz, DMSO-d6) δ 11.70 (s, 1H), 9.15 (s, 1H), 8.60 (d, J=8.8 Hz, 1H), 8.06 (d, J=8.4 Hz, 2H), 7.96 (d, J=8.8 Hz, 2H), 7.79 (dd, J=8.6, 2.2 Hz, 2H), 7.16 (d, J=8.4 Hz, 2H), 4.65 (s, 2H), 3.87 (s, 3H), 2.63 (s, 3H). [M+H]+: 401.
    • Example 205 N-(7-(4-fluorophenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00216
  • 1H NMR (400 MHz, DMSO-d6) δ 11.74 (s, 1H), 9.13 (s, 1H), 8.57 (d, J=8.4 Hz, 1H), 7.99 (d, J=8.4 Hz, 2H), 7.72-7.61 (m, 6H), 7.32 (t, J=8.8 Hz, 2H), 4.60 (s, 2H). [M+H]+: 347.
    • Example 206 N-(7-(4-(dimethylamino)phenyl)-3-oxoisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00217
  • 1H NMR (400 MHz, DMSO-d6) δ 11.72 (s, 1H), 9.08 (s, 1H), 8.53 (d, J=8.4 Hz, 1H), 7.98 (d, J=6.8 Hz, 2H), 7.67-7.60 (m, 4H), 7.46 (d, J=8.4 Hz, 2H), 6.82 (d, J=9.2 Hz, 2H), 4.59 (s, 2H), 2.95 (s, 6H). [M+H]+: 372.
    • Example 207 N-(7-(4-cyanophenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00218
  • 1H NMR (400 MHz, DMSO-d6) δ 11.79 (s, 1H), 9.18 (s, 1H), 8.61 (d, J=8.4 Hz, 1H), 8.00-7.95 (m, 4H), 7.83 (dd, J=8.4, 14.4 Hz, 3H), 7.71-7.62 (m, 3H), 4.65 (s, 2H). [M+H]+: 354.
    • Example 208 4-Cyano-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00219
  • 1H NMR (400 MHz, DMSO-d6) δ 11.82 (s, 1H), 9.16 (s, 1H), 8.54 (d, J=8.4 Hz, 1H), 8.12 (s, 4H), 7.74 (d, J=8.4 Hz, 1H), 7.63 (d, J=8.4 Hz, 2H), 7.50 (t, J=7.6 Hz, 2H), 7.41 (t, J=7.4 Hz, 1H), 4.62 (s, 2H). [M+H]+: 354.
    • Example 209 N-(3-oxo-7-(p-tolyl)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00220
  • 1H NMR (400 MHz, DMSO-d6) δ 11.74 (s, 1H), 9.11 (s, 1H), 8.57 (d, J=8.0 Hz, 1H), 7.99 (d, J=7.2 Hz, 2H), 7.71-7.61 (m, 4H), 7.52 (d, J=8.0 Hz, 2H), 7.30 (d, J=8.0 Hz, 2H), 4.60 (s, 2H), 2.36 (s, 3H). [M+H]+: 343.
    • Example 210 N-(3-oxo-7-(4-(trifluoromethyl)phenyl)isoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00221
  • 1H NMR (400 MHz, DMSO-d6) δ 11.78 (s, 1H), 9.17 (s, 1H), 8.61 (d, J=8.4 Hz, 1H), 7.99 (d, J=7.2 Hz, 2H), 7.88-7.79 (m, 5H), 7.69-7.62 (m, 3H), 4.65 (s, 2H). [M+H]+: 397.
    • Example 211 N-(3-oxo-7-phenylisoindolin-4-yl)isonicotinamide
  • Figure US20160311772A1-20161027-C00222
  • 1H NMR (400 MHz, DMSO-d6) δ 11.84 (s, 1H), 9.16 (s, 1H), 8.88 (d, J=5.6 Hz, 2H), 8.54 (d, J=8.4 Hz, 1H), 7.86 (d, J=6.0 Hz, 2H), 7.74 (d, J=8.8 Hz, 1H), 7.63 (d, J=7.2 Hz, 2H), 7.50 (t, J=7.4 Hz, 2H), 7.41 (d, J=7.4 Hz, 1H), 4.62 (s, 2H). [M+H]+: 330.
    • Example 212 N-(3-oxo-7-phenylisoindolin-4-yl)furan-2-carboxamide
  • Figure US20160311772A1-20161027-C00223
  • 1H NMR (400 MHz, DMSO-d6) δ 11.59 (s, 1H), 9.05 (s, 1H), 8.53 (d, J=8.4 Hz, 1H), 8.03 (s, 1H), 7.70 (d, J=8.4 Hz, 1H), 7.62 (d, J=7.2 Hz, 2H), 7.49 (d, J=7.4 Hz, 2H), 7.42-7.40 (m, 1H), 7.31 (d, J=3.2 Hz, 1H), 6.78-6.77 (m, 1H), 4.59 (s, 2H). [M+H]+: 319.
    • Example 213 N-(3-oxo-7-phenylisoindolin-4-yl)nicotinamide
  • Figure US20160311772A1-20161027-C00224
  • 1H NMR (400 MHz, DMSO-d6) δ 11.79 (s, 1H), 9.16 (s, 2H), 8.84 (dd, J=1.6, 4.8 Hz, 1H), 8.54 (d, J=8.4 Hz, 1H), 8.32 (d, J=8.0 Hz, 1H), 7.74 (d, J=8.4 Hz, 1H), 7.69-7.62 (m, 3H), 7.50 (t, J=7.6 Hz, 2H), 7.43-7.41 (m, 1H), 4.62 (s, 2H). [M+H]+: 330.
    • Example 214 4-Fluoro-N-(3-oxo-7-(quinolin-6-yl)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00225
  • 1H NMR (400 MHz, DMSO-d6) δ 11.76 (s, 1H), 9.20 (s, 1H), 8.94 (d, J=4.2 Hz, 1H), 8.61 (d, J=8.4 Hz, 1H), 8.46 (d, J=8.3 Hz, 1H), 8.26 (d, J=2.0 Hz, 1H), 8.12 (d, J=8.7 Hz, 1H), 8.05 (dt, J=9.0, 4.5 Hz, 3H), 7.89 (d, J=8.5 Hz, 1H), 7.60 (dd, J=8.3, 4.4 Hz, 1H), 7.48 (t, J=8.6 Hz, 2H), 4.73 (s, 2H); [M+H]+: 398.
    • Example 215 4-Fluoro-N-(3-oxo-7-(quinolin-5-yl)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00226
  • 1H NMR (400 MHz, DMSO-d6) δ 11.69 (s, 1H), 9.05 (s, 1H), 8.96 (dd, J=4.1, 1.6 Hz, 1H), 8.61 (d, J=8.3 Hz, 1H), 8.12 (dt, J=8.5, 1.1 Hz, 1H), 8.10-8.03 (m, 3H), 7.86 (dd, J=8.5, 7.1 Hz, 1H), 7.71 (dd, J=7.1, 1.2 Hz, 1H), 7.64 (d, J=8.3 Hz, 1H), 7.55-7.47 (m, 3H), 4.34 (s, 2H); [M+H]+: 398.
    • Example 216 4-Fluoro-N-(3-oxo-7-(quinolin-4-yl)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00227
  • 1H NMR (400 MHz, DMSO-d6) δ 11.71 (s, 1H), 9.09 (s, 1H), 8.99 (d, J=4.3 Hz, 1H), 8.64 (d, J=8.4 Hz, 1H), 8.14 (dd, J=8.6, 1.2 Hz, 1H), 8.10-8.05 (m, 2H), 7.83 (ddd, J=8.4, 6.8, 1.4 Hz, 1H), 7.74 (dd, J=8.5, 1.3 Hz, 1H), 7.71 (d, J=8.4 Hz, 1H), 7.64 (d, J=4.5 Hz, 1H), 7.62-7.58 (m, 1H), 7.53-7.46 (m, 2H), 4.30 (s, 2H); [M+H]+: 398.
    • Example 217 N-(7-(1H-indol-7-yl)-3-oxoisoindolin-4-yl)-4-fluorobenzamide
  • Figure US20160311772A1-20161027-C00228
  • 1H NMR (400 MHz, DMSO-d6) δ 11.73 (s, 1H), 10.95 (s, 1H), 9.04 (s, 1H), 8.60 (d, J=8.3 Hz, 1H), 8.08 (dd, J=8.5, 5.3 Hz, 2H), 7.73 (d, J=8.4 Hz, 1H), 7.61 (d, J=7.7 Hz, 1H), 7.50 (t, J=8.6 Hz, 2H), 7.33 (t, J=2.8 Hz, 1H), 7.14 (dd, J=20.1, 7.3 Hz, 2H), 6.54 (t, J=2.3 Hz, 1H), 4.33 (s, 2H); [M+H]+: 386.
    • Example 218 N-(7-(1H-benzo[d]imidazol-4-yl)-3-oxoisoindolin-4-yl)-4-fluorobenzamide
  • Figure US20160311772A1-20161027-C00229
  • 1H NMR (400 MHz, DMSO-d6) δ 12.65 (s, 1H), 11.74 (s, 1H), 9.03 (s, 1H), 8.57 (d, J=8.4 Hz, 1H), 8.28 (s, 1H), 8.10-8.03 (m, 2H), 7.85 (d, J=21.9 Hz, 1H), 7.62 (s, 1H), 7.53-7.44 (m, 2H), 7.33 (q, J=3.2, 2.5 Hz, 2H), 4.57 (s, 2H); [M+H]+: 387.
    • Example 219 N-(7-benzyl-3-oxoisoindolin-4-yl)-4-fluorobenzamide
  • Figure US20160311772A1-20161027-C00230
  • 1H NMR (400 MHz, DMSO-d6) δ 11.44 (br s, 1H), 8.94 (br s, 1H), 8.37 (d, J=8.4 Hz, 1H), 8.02-7.98 (m, 2H), 7.47-7.42 (m, 3H), 7.32-7.28 (m, 2H), 7.25-7.19 (m, 3H), 4.29 (s, 2H), 4.00 (s, 2H); [M+H]+: 361.
    • Example 220 (R)-tert-butyl 2-((3-oxo-7-phenylisoindolin-4-yl)carbamoyl) pyrrolidine-1-carboxylate
  • Figure US20160311772A1-20161027-C00231
  • 1H NMR (400 MHz, DMSO-d6) δ 10.89 (s, 1H), 10.77 (s, 1H), 9.03 (d, J=10.4 Hz, 2H), 8.29 (d, J=8.7 Hz, 2H), 7.74 (dd, J=8.7, 4.0 Hz, 2H), 4.32 (s, 2H), 4.21-4.15 (m, 2H), 3.56-3.54 (m, 1H), 3.52-3.46 (m, 1H), 3.43-3.39 (m, 2H), 1.97-1.94 (m, 2H), 1.23 (s, 9H); [M+H]+: 422.
    • Example 221 (R)—N-(3-oxo-7-phenylisoindolin-4-yl)pyrrolidine-2-carboxamide
  • Figure US20160311772A1-20161027-C00232
  • 1H NMR (400 MHz, DMSO-d6) δ 11.78 (s, 1H), 10.91 (s, 1H), 8.85 (s, 1H), 8.42 (d, J=8.7 Hz, 2H), 7.71 (dd, J=8.7, 5.4 Hz, 2H), 4.28 (s, 2H), 4.25-4.20 (m, 1H), 4.77 (dd, J=9.1, 5.0 Hz, 2H), 3.01-2.95 (m, 2H), 2.84-2.78 (m, 2H), 2.09-2.00 (m, 2H); [M+H]+: 322.
    • Example 222 3-Amino-N-(2-methyl-3-oxo-7-phenylisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00233
  • [M+H]+: 358.
  • 1H NMR (400 MHz, DMSO-d6) δ 11.49 (s, 1H), 8.58 (d, J=8.0 Hz, 1H), 7.69 (d, J=8.4 Hz, 1H), 7.61-7.59 (m, 2H), 7.52-7.48 (m, 2H), 7.43-7.39 (m, 1H), 7.25-7.20 (m, 2H), 7.11-7.09 (m, 1H), 6.83-6.80 (m, 1H), 5.45 (br s, 2H), 4.69 (s, 2H), 3.11 (s, 3H); MS (ESI) m/z 358 (M+H)+.
    • Example 223 2-Amino-N-(2-methyl-3-oxo-7-phenylisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00234
  • [M+H]+: 358.
  • 1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 8.55 (d, J=8.4 Hz, 1H), 7.68 (d, J=8.4 Hz, 1H), 7.65-7.59 (m, 3H), 7.52-7.48 (m, 2H), 7.43-7.39 (m, 1H), 7.29-7.25 (m, 1H), 6.83 (d, J=8.0 Hz, 1H), 6.72-6.64 (m, 3H), 4.69 (s, 2H), 3.11 (s, 3H); MS (ESI) m/z 358 (M+H)+.
    • Example 224 N-(7-(2,3-dimethoxyphenyl)-2-(furan-2-carbonyl)-3-oxoisoindolin-4-yl)furan-2-carboxamide
  • Figure US20160311772A1-20161027-C00235
  • 1H NMR (400 MHz, DMSO-d6) δ 11.03 (br s, 1H), 8.59 (d, J=8.4 Hz, 1H), 8.07 (dd, J=3.6, 1.2 Hz, 1H), 7.72 (d, J=8.4 Hz, 1H), 7.64 (d, J=3.2 Hz, 1H), 7.37 (d, J=3.6 Hz, 1H), 7.22-7.14 (m, 2H), 6.97 (dd, J=7.2, 1.6 Hz, 1H), 6.79-6.77 (m, 2H), 4.89 (s, 2H), 3.87 (s, 3H), 3.49 (s, 3H); [M+H]+: 473.
    • Example 225 N-(7-(2,3-dimethoxyphenyl)-3-oxo-2-(thiophene-2-carbonyl) isoindolin-4-yl)thiophene-2-carboxamide
  • Figure US20160311772A1-20161027-C00236
  • 1H NMR (400 MHz, DMSO-d6) δ 10.95 (br s, 1H), 8.48 (d, J=8.4 Hz, 1H), 8.13 (dd, J=3.8, 1.0 Hz, 1H), 8.04 (dd, J=5.0, 1.0 Hz, 1H), 7.99 (dd, J=5.0, 1.0 Hz, 1H), 7.79 (d, J=3.6 Hz, 1H), 7.73 (d, J=8.4 Hz, 1H), 7.32-7.29 (m, 1H), 7.28-7.25 (m, 1H), 7.23-7.15 (m, 2H), 6.97 (dd, J=7.4, 1.8 Hz, 1H), 4.90 (s, 2H), 3.88 (s, 3H), 3.50 (s, 3H); [M+H]+: 505.
    • Example 226 1-(4-Fluorophenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea
  • Figure US20160311772A1-20161027-C00237
  • To a mixture of 7-amino-4-phenylisoindolin-1-one 16 (100 mg, 0.45 mmol) in THF (4 mL) was slowly added TEA (186 μL, 1.34 mmol) and 4-fluorophenyl isocyanate (61 μL, 0.54 mol) at 0° C. After warming the mixture to room temperature, the mixture was stirred for 12 hours. The solid thus obtained was washed with water to provide the title compound 27 (117 mg, 73%) as a white solid.
  • 1H NMR (400 MHz, DMSO-d6) δ 9.53 (br s, 1H), 8.76 (br s, 1H), 8.30 (d, J=8.0 Hz, 1H), 7.57-7.51 (m, 4H), 7.45 (t, J=7.6 Hz, 2H), 7.35 (t, J=7.2 Hz, 1H), 4.49 (s, 2H), 3.08 (q, J=6.4 Hz, 2H), 1.43 (q, J=7.2 Hz, 2H), 1.35-1.29 (m, 2H), 0.90 (t, J=7.4 Hz, 3H); [M+H]+: 324.
  • The following compounds of Examples 227 to 246 were obtained by using corresponding starting materials and repeating the procedure of Example 226.
    • Example 227 1-(3-Oxo-7-phenylisoindolin-4-yl)-3-phenylurea
  • Figure US20160311772A1-20161027-C00238
  • 1H NMR (400 MHz, DMSO-d6) δ 9.96 (br s, 1H), 9.86 (br s, 1H), 8.86 (s, 1H), 8.35 (d, J=8.4 Hz, 1H), 7.61-7.53 (m, 5H), 7.47 (t, J=7.8 Hz, 2H), 7.36-7.35 (m, 1H), 7.29 (t, J=7.8 Hz, 2H), 7.01-6.97 (m, 1H), 4.53 (s, 2H); [M+H]+: 344.
    • Example 228 1-(4-Cyanophenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea
  • Figure US20160311772A1-20161027-C00239
  • 1H NMR (400 MHz, DMSO-d6) δ 10.48 (br s, 1H), 10.03 (br s, 1H), 8.92 (s, 1H), 8.35 (d, J=8.4 Hz, 1H), 7.75-7.74 (m, 4H), 7.64-7.58 (m, 3H), 7.49-7.45 (m, 2H), 7.40-7.38 (m, 1H), 4.55 (s, 2H); [M+H]+: 369.
    • Example 229 1-Butyl-3-(3-oxo-7-phenylisoindolin-4-yl)urea
  • Figure US20160311772A1-20161027-C00240
  • 1H NMR (400 MHz, DMSO-d6) δ 9.53 (br s, 1H), 8.76 (br s, 1H), 8.30 (d, J=8.0 Hz, 1H), 7.57-7.51 (m, 4H), 7.45 (t, J=7.6 Hz, 2H), 7.35 (t, J=7.2 Hz, 1H), 4.49 (s, 2H), 3.08 (q, J=6.4 Hz, 2H), 1.43 (q, J=7.2 Hz, 2H), 1.35-1.29 (m, 2H), 0.90 (t, J=7.4 Hz, 3H); [M+H]+: 324.
    • Example 230 1-(4-Methoxyphenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea
  • Figure US20160311772A1-20161027-C00241
  • 1H NMR (400 MHz, DMSO-d6) δ 9.80 (br s, 1H), 9.75 (br s, 1H), 8.83 (br s, 1H), 8.34 (d, J=8.4 Hz, 1H), 7.59-7.57 (m, 3H), 7.49-7.43 (m, 4H), 7.39-7.35 (m, 1H), 6.88 (d, J=9.2 Hz, 2H), 4.53 (s, 2H); [M+H]+: 374.
    • Example 231 1-Cyclohexyl-3-(3-oxo-7-phenylisoindolin-4-yl)urea
  • Figure US20160311772A1-20161027-C00242
  • 1H NMR (400 MHz, DMSO-d6) δ 9.46 (br s, 1H), 8.75 (br s, 1H), 8.30 (d, J=8.8 Hz, 1H), 7.57-7.53 (m, 2H), 7.51-7.43 (m, 4H), 7.37-7.33 (m, 1H), 4.49 (s, 2H), 3.49-3.42 (m, 1H), 1.83-1.79 (m, 2H), 1.72-1.68 (m, 2H), 1.58-1.54 (m, 1H), 1.33-1.11 (m, 5H); [M+H]+: 350.
    • Example 232 1-(3-Oxo-7-phenylisoindolin-4-yl)-3-(p-tolyl)urea
  • Figure US20160311772A1-20161027-C00243
  • 1H NMR (400 MHz, DMSO-d6) δ 9.83-9.82 (m, 2H), 8.81 (br s, 1H), 8.35 (d, J=8.8 Hz, 1H), 7.59-7.57 (m, 3H), 7.49-7.37 (m, 5H), 7.10 (d, J=8.4 Hz, 2H), 4.52 (s, 2H), 2.25 (s, 3H); [M+H]+: 358.
    • Example 233 1-(2-Methoxyphenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea
  • Figure US20160311772A1-20161027-C00244
  • 1H NMR (400 MHz, DMSO-d6) δ 9.87 (br s, 1H), 9.22 (br s, 1H), 8.71 (br s, 1H), 8.27 (d, J=8.4 Hz, 1H), 7.85 (d, J=7.6 Hz, 1H), 7.59-7.55 (m, 3H), 7.47 (t, J=7.6 Hz, 2H), 7.37 (t, J=7.4 Hz, 1H), 7.04-7.03 (m, 2H), 6.93-6.88 (m, 1H), 4.50 (s, 2H), 3.85 (s, 3H); [M+H]+: 374.
    • Example 234 1-Isopropyl-3-(3-oxo-7-phenylisoindolin-4-yl)urea
  • Figure US20160311772A1-20161027-C00245
  • 1H NMR (400 MHz, DMSO-d6) δ 9.46 (br s, 1H), 8.71 (br s, 1H), 8.30 (d, J=8.4 Hz, 1H), 7.56-7.51 (m, 3H), 7.47-7.43 (m, 3H), 7.37-7.34 (m, 1H), 4.48 (s, 2H), 3.81-3.76 (m, 1H), 1.11 (d, J=6.4 Hz, 6H); [M+H]+: 310.
    • Example 235 1-(4-Nitrophenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea
  • Figure US20160311772A1-20161027-C00246
  • 1H NMR (400 MHz, DMSO-d6) δ 10.68 (br s, 1H), 10.08 (br s, 1H), 8.89 (br s, 1H), 8.36 (d, J=8.4 Hz, 1H), 8.21 (d, J=9.2 Hz, 2H), 7.80 (d, J=9.2 Hz, 2H), 7.63 (d, J=8.4 Hz, 1H), 8.36 (d, J=7.6 Hz, 2H), 7.48 (t, J=8.4 Hz, 2H), 8.36 (d, J=8.4 Hz, 1H), 7.38 (t, J=7.4 Hz, 1H), 4.54 (s, 2H); [M+H]+: 389.
    • Example 236 1-Ethyl-3-(3-oxo-7-phenylisoindolin-4-yl)urea
  • Figure US20160311772A1-20161027-C00247
  • 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 8.72 (s, 1H), 8.30 (d, J=8.5 Hz, 1H), 7.60-7.49 (m, 4H), 7.46 (t, J=7.6 Hz, 2H), 7.36 (t, J=7.3 Hz, 1H), 4.49 (s, 2H), 3.17-3.05 (m, 2H), 1.07 (t, J=7.2 Hz, 3H); [M+H]+: 296.
    • Example 237 1-(4-Acetylphenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea
  • Figure US20160311772A1-20161027-C00248
  • 1H NMR (400 MHz, DMSO-d6) δ 10.37 (s, 1H), 9.99 (s, 1H), 8.86 (s, 1H), 8.36 (d, J=8.5 Hz, 1H), 7.92 (d, J=8.4 Hz, 2H), 7.69 (d, J=8.4 Hz, 2H), 7.60 (dd, J=10.5, 7.8 Hz, 3H), 7.48 (t, J=7.5 Hz, 2H), 7.38 (t, J=7.3 Hz, 1H), 4.54 (s, 2H), 2.53 (s, 3H); [M+H]+: 386.
    • Example 238 1-(3-Oxo-7-phenylisoindolin-4-yl)-3-(o-tolyl)urea
  • Figure US20160311772A1-20161027-C00249
  • 1H NMR (400 MHz, DMSO-d6) δ 9.86 (s, 1H), 9.16 (s, 1H), 8.76 (s, 1H), 8.32 (d, J=8.5 Hz, 1H), 7.61-7.54 (m, 3H), 7.46 (q, J=7.4 Hz, 3H), 7.37 (t, J=7.3 Hz, 1H), 7.25-7.12 (m, 2H), 7.06 (t, J=7.2 Hz, 1H), 4.51 (s, 2H), 2.26 (s, 3H); [M+H]+: 358.
    • Example 239 1-Cyclopentyl-3-(3-oxo-7-phenylisoindolin-4-yl)urea
  • Figure US20160311772A1-20161027-C00250
  • 1H NMR (400 MHz, DMSO-d6) δ 9.47 (s, 1H), 8.71 (s, 1H), 8.31 (d, J=8.6 Hz, 1H), 7.59-7.49 (m, 4H), 7.45 (t, J=7.5 Hz, 2H), 7.35 (t, J=7.3 Hz, 1H), 4.48 (s, 2H), 3.96 (q, J=6.6 Hz, 1H), 1.87-1.79 (m, 2H), 1.66 (s, 2H), 1.52 (s, 2H), 1.48-1.38 (m, 2H); [M+H]+: 336.
    • Example 240 1-(3-Fluorophenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea
  • Figure US20160311772A1-20161027-C00251
  • 1H NMR (400 MHz, DMSO-d6) δ 10.17 (s, 1H), 9.92 (s, 1H), 8.85 (s, 1H), 8.35 (d, J=8.6 Hz, 1H), 7.64-7.43 (m, 6H), 7.38 (t, J=7.4 Hz, 1H), 7.37-7.22 (m, 2H), 6.81 (s, 1H), 4.53 (s, 2H); [M+H]+: 362.
    • Example 241 1-(3-(Methylthio)phenyl)-3-(3-oxo-7-phenylisoindolin-4-yl) urea
  • Figure US20160311772A1-20161027-C00252
  • 1H NMR (400 MHz, DMSO-d6) δ 9.98 (s, 1H), 9.88 (s, 1H), 8.83 (s, 1H), 8.35 (d, J=8.4 Hz, 1H), 7.69-7.58 (m, 3H), 7.53 (s, 1H), 7.47 (t, J=7.6 Hz, 2H), 7.37 (t, J=7.2 Hz, 1H), 7.30 (d, J=8.4 Hz, 1H), 7.22 (d, J=7.8 Hz, 1H), 6.88 (d, J=7.6 Hz, 1H), 4.53 (s, 2H), 2.46 (s, 3H). [M+H]+: 390.
    • Example 242 1-(2-Fluorophenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea
  • Figure US20160311772A1-20161027-C00253
  • 1H NMR (400 MHz, DMSO-d6) δ 9.96 (s, 1H), 9.80 (s, 1H), 8.78 (s, 1H), 8.30 (d, J=8.4 Hz, 1H), 7.91 (d, J=8.2 Hz, 1H), 7.59-7.57 (m, 3H), 7.49-7.45 (m, 2H), 7.39-7.35 (m, 1H), 7.26-7.09 (m, 3H), 4.52 (s, 2H). [M+H]+: 362.
    • Example 243 1-(4-Chlorophenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea
  • Figure US20160311772A1-20161027-C00254
  • 1H NMR (400 MHz, DMSO-d6) δ 10.08 (s, 1H), 9.90 (s, 1H), 8.84 (s, 1H), 8.34 (d, J=8.4 Hz, 1H), 7.61-7.56 (m, 5H), 7.47 (t, J=7.6 Hz, 2H), 7.38 (d, J=7.2 Hz, 1H), 7.34 (d, J=8.8 Hz, 2H), 4.53 (s, 2H). [M+H]+: 378.
    • Example 244 1-(7-(4-Methoxyphenyl)-3-oxoisoindolin-4-yl)-3-phenylurea
  • Figure US20160311772A1-20161027-C00255
  • 1H NMR (400 MHz, DMSO-d6) δ 9.93 (s, 1H), 9.83 (s, 1H), 8.84 (s, 1H), 8.32 (d, J=8.4 Hz, 1H), 7.56-7.51 (m, 5H), 7.29 (dd, J=8.0, 7.6 Hz, 2H), 7.04-7.01 (m, 3H), 4.51 (s, 2H), 3.80 (s, 3H). [M+H]+: 374.
    • Example 245 1-(7-(4-Fluorophenyl)-3-oxoisoindolin-4-yl)-3-phenylurea
  • Figure US20160311772A1-20161027-C00256
  • 1H NMR (400 MHz, DMSO-d6) δ 9.96 (s, 1H), 9.86 (s, 1H), 8.88 (s, 1H), 8.35 (d, J=8.4 Hz, 1H), 7.65-7.54 (m, 4H), 7.32-7.27 (m, 3H), 6.99 (t, J=7.2 Hz, 2H), 4.52 (s, 2H). [M+H]+: 362.
    • Example 246 7-Amino-N-cyclohexyl-1-oxo-4-phenylisoindolin-2-carboxamide
  • Figure US20160311772A1-20161027-C00257
  • 1H NMR (400 MHz, DMSO-d6) δ 8.44 (d, J=7.6 Hz, 1H), 7.51-7.49 (m, 2H), 7.46-7.42 (m, 3H), 7.34-7.30 (m, 1H), 6.77 (d, J=8.4 Hz, 1H), 6.48 (br s, 2H), 4.80 (s, 2H), 1.87-1.82 (m, 2H), 1.66-1.62 (m, 2H), 1.55-1.52 (m, 1H), 1.40-1.23 (m, 6H); [M+H]+: 350.
    • Example 247 1-(3-Oxo-7-phenylisoindolin-4-yl)-3-phenylthiourea
  • Figure US20160311772A1-20161027-C00258
  • To a mixture of 7-amino-4-phenylisoindolin-1-one 16 (100 mg, 0.45 mmol) in THF (4 mL) was slowly added NMM (150 μL, 1.35 mmol) and phenyl isothiocyanate (61 μL, 0.54 mol) at 0° C. After warming the mixture to room temperature, the mixture was stirred for 12 hours. The solid thus obtained was washed with water to give the title compound 29 (41 mg, 25%) as a white solid.
  • 1H NMR (400 MHz, DMSO-d6) δ 10.87 (br s, 1H), 10.67 (br s, 1H), 8.96 (d, J=8.4 Hz, 1H), 8.87 (br s, 1H), 7.63-7.58 (m, 3H), 7.50-7.46 (m, 4H), 7.23-7.19 (m, 3H), 7.21 (t, J=7.4 Hz, 1H), 4.53 (s, 2H); [M+H]+: 360.
    • Example 248 Phenyl (3-oxo-7-phenylisoindolin-4-yl)carbamate
  • Figure US20160311772A1-20161027-C00259
  • To a mixture of 7-amino-4-phenylisoindolin-1-one 16 (100 mg, 0.45 mmol) in CH2Cl2/pyridine (2/0.4 mL) was slowly added phenyl chloroformate (61 μL, 0.49 mmol) at 0° C. After warming the mixture to room temperature, the mixture was stirred for 1 hour. The solid thus obtained was washed with CH2Cl2 to provide the title compound 31 (45 mg, 29%) as a white solid.
  • 1H NMR (400 MHz, DMSO-d6) δ 10.46 (br s, 1H), 9.07 (br s, 1H), 8.10 (d, J=8.4 Hz, 1H), 7.70 (d, J=8.8 Hz, 1H), 7.62-7.59 (m, 2H), 7.51-7.44 (m, 4H), 7.42-7.37 (m, 1H), 7.32-7.28 (m, 3H), 4.59 (s, 2H); [M+H]+: 345.
    • Example 249 N-(3-oxo-7-phenylisoindolin-4-yl)benzenesulfonamide
  • Figure US20160311772A1-20161027-C00260
  • To a mixture of 7-amino-4-phenylisoindolin-1-one 16 (100 mg, 0.45 mmol) in THF (2.2 mL) was slowly added NMM (0.15 mL, 1.34 mmol) and benzenesulfonyl chloride (86 μL, 0.67 mol) at 0° C. The reaction mixture was stirred at room temperature for 12 hours, and then poured into water at 0° C. The solid thus obtained was washed with water to give N-(3-oxo-7-phenylisoindolin-4-yl)benzenesulfonamide 33 (150 mg, 94%) as a white solid.
  • 1H NMR (400 MHz, DMSO-d6) δ 10.38 (s, 1H), 9.05 (s, 1H), 7.93 (d, J=7.6 Hz, 2H), 7.69-7.65 (m, 1H), 7.62-7.58 (m, 2H), 7.53-7.49 (m, 2H), 7.47-7.42 (m, 2H), 7.38-7.35 (m, 1H), 4.50 (s, 2H). [M+H]+: 365.
  • The following compounds of Examples 250 to 252 were obtained by using corresponding starting materials and repeating the procedure of Example 249.
    • Example 250 N-(3-oxo-7-phenylisoindolin-4-yl)methanesulfonamide
  • Figure US20160311772A1-20161027-C00261
  • 1H NMR (400 MHz, DMSO-d6) δ 9.87 (s, 1H), 9.05 (s, 1H), 7.67 (d, J=8.4 Hz, 1H), 7.59 (d, J=7.6 Hz, 2H), 7.52-7.47 (m, 3H), 7.42-7.38 (m, 1H), 4.57 (s, 2H), 3.25 (s, 3H). [M+H]+: 303.
    • Example 251 4-Fluoro-N-(3-oxo-7-phenylisoindolin-4-yl)benzene sulfonamide
  • Figure US20160311772A1-20161027-C00262
  • 1H NMR (400 MHz, DMSO-d6) δ 10.38 (s, 1H), 9.06 (s, 1H), 8.02-7.99 (m, 2H), 7.61 (d, J=8.0 z, 1H), 7.54d, J=7.2 Hz, 2H), 7.49-7.42 (m, 5H), 7.39-7.35 (m, 3H), 4.51 (s, 2H). [M+H]+: 383.
    • Example 252 4-Methoxy-N-(3-oxo-7-phenylisoindolin-4-yl)benzene sulfonamide
  • Figure US20160311772A1-20161027-C00263
  • 1H NMR (400 MHz, DMSO-d6) δ 10.28 (s, 1H), 9.04 (s, 1H), 7.85 (d, J=8.8 Hz, 2H), 7.59 (d, J=8.4 Hz, 1H), 7.53 (d, J=7.2 Hz, 2H), 7.48-7.43 (m, 3H), 7.39-7.35 (m, 1H), 7.10 (d, J=9.2 Hz, 2H), 4.50 (s, 2H), 3.80 (s, 3H). [M+H]+: 395.
    • Example 253 7-((2-Chloroethyl)amino)-4-phenylisoindolin-1-one
  • Figure US20160311772A1-20161027-C00264
  • To a mixture of 7-amino-4-phenylisoindolin-1-one 16 (800 mg, 3.57 mmol) and NaBH3CN (450 mg, 7.13 mmol) in methanol (18 mL) was added chloroacetaldehyde (0.7 mL, 5.35 mmol) and HCl (in methanol solution, 1.25M 5.7 mL) at 0° C. The reaction mixture was stirred at room temperature for 12 hours, and then poured to water at 0° C. The precipitate was washed with water to give the title compound (940 mg, 92%) as a white solid.
  • 1H NMR (400 MHz, DMSO-d6) δ 8.42 (s, 1H), 7.54-7.49 (m, 2H), 7.44-7.40 (m, 3H), 7.30 (t, J=7.4 Hz, 1H), 7.20 (d, J=6.2 Hz, 1H), 6.78 (d, J=8.4 Hz, 1H), 4.43 (s, 2H), 3.81 (t, J=6.0 Hz, 2H), 3.62 (q, J=6.0 Hz, 2H). [M+H]+: 287.
    • Example 254 3-((3-Oxo-7-phenylisoindolin-4-yl)amino)propanenitrile
  • Figure US20160311772A1-20161027-C00265
  • A mixture of 7-((2-chloroethyl)amino)-4-phenylisoindolin-1-one 35 (100 mg, 0.35 mmol) and KCN (34 mg, 0.52 mmol) in DMF (1.7 mL) was stirred at 80° C. for 12 hours. The reaction mixture was poured to ice water, filtered, washed with water, and dried to give the title compound 36 (89 mg, 92%).
  • 1H NMR (400 MHz, DMSO-d6) δ 8.43 (s, 1H), 7.52-7.50 (m, 2H), 7.45-7.40 (m, 3H), 7.30 (t, J=7.4 Hz, 1H), 7.16 (t, J=6.6 Hz, 1H), 6.82 (d, J=8.4 Hz, 1H), 4.44 (s, 2H), 3.59 (q, J=6.4 Hz, 2H), 2.81 (t, J=6.4 Hz, 2H). [M+H]+: 278.
  • The following compounds of Examples 255 to 270 were obtained by using corresponding starting materials and repeating the procedure of Example 254.
    • Example 255 7-((2-(Dimethylamino)ethyl)amino)-4-phenylisoindolin-1-one
  • Figure US20160311772A1-20161027-C00266
  • 1H NMR (400 MHz, DMSO-d6) δ 8.34 (s, 1H), 7.49 (d, J=7.2 Hz, 2H), 7.41 (t, J=8.0 Hz, 3H), 7.29 (t, J=7.2 Hz, 1H), 7.02 (t, J=5.4 Hz, 1H), 6.68 (d, J=8.4 Hz, 1H), 4.42 (s, 2H), 3.26 (q, J=6.0 Hz, 2H), 2.49 (t, J=6.0 Hz, 2H), 2.19 (s, 6H). [M+H]+: 296.
    • Example 256 7-((2-Hydroxyethyl)amino)-4-phenylisoindolin-1-one
  • Figure US20160311772A1-20161027-C00267
  • 1H NMR (400 MHz, DMSO-d6) δ 8.36 (s, 1H), 7.49 (d, J=7.6 Hz, 2H), 7.43-7.39 (m, 3H), 7.49 (t, J=7.6 Hz, 1H), 7.06 (t, J=5.4 Hz, 1H), 6.70 (d, J=8.8 Hz, 1H), 4.86 (br, s, 1H), 4.42 (s, 2H), 3.61 (t, J=5.6 Hz, 2H), 3.27 (t, J=5.6 Hz, 2H), 2.19 (s, 6H). [M+H]+: 269.
    • Example 257 2-(2-((3-Oxo-7-phenylisoindolin-4-yl)amino)ethyl)isoindolin-1,3-dione
  • Figure US20160311772A1-20161027-C00268
  • 1H NMR (400 MHz, DMSO-d6) δ 8.33 (s, 1H), 7.88-7.81 (m, 4H), 7.48-7.46 (m, 2H), 7.43-7.38 (m, 3H), 7.29 (t, J=7.2 Hz, 1H), 7.09 (t, J=6.6 Hz, 1H), 6.80 (d, J=8.8 Hz, 1H), 4.40 (s, 2H), 3.79 (t, J=6.2 Hz, 2H), 3.55 (q, J=6.4 Hz, 2H). [M+H]+: 398.
    • Example 258 7-((2-(4-Methylpiperazin-1-yl)ethyl)amino)-4-phenylisoindolin-1-one
  • Figure US20160311772A1-20161027-C00269
  • 1H NMR (400 MHz, DMSO-d6) δ 8.29 (s, 1H), 7.49 (d, J=6.8 Hz, 2H), 7.43-7.39 (m, 3H), 7.29 (t, J=7.2 Hz, 1H), 7.08 (t, J=5.2 Hz, 1H), 6.68 (d, J=8.8 Hz, 1H), 4.41 (s, 2H), 3.29 (q, J=5.6 Hz, 2H), 2.56 (t, J=6.4 Hz, 2H), 2.43 (br.s, 4H), 2.33 (br.s, 4H), 2.15 (s, 3H). [M+H]+: 351.
    • Example 259 4-Phenyl-7-((2-(piperidin-1-yl)ethyl)amino)isoindolin-1-one
  • Figure US20160311772A1-20161027-C00270
  • 1H NMR (400 MHz, DMSO-d6) δ 8.28 (s, 1H), 7.49 (d, J=7.2 Hz, 2H), 7.43-7.39 (m, 3H), 7.29 (t, J=7.4 Hz, 1H), 7.10 (t, J=5.4 Hz, 1H), 6.67 (d, J=8.4 Hz, 1H), 4.41 (s, 2H), 3.27 (q, J=6.0 Hz, 2H), 2.52 (t, J=6.4 Hz, 2H), 2.38 (br.s, 4H), 1.53-1.49 (m, 4H), 1.42-1.39 (m, 2H). [M+H]+: 336.
    • Example 260 7-((2-Morpholinoethyl)amino)-4-phenylisoindolin-1-one
  • Figure US20160311772A1-20161027-C00271
  • 1H NMR (400 MHz, DMSO-d6) δ 8.30 (s, 1H), 7.49 (d, J=7.2 Hz, 2H), 7.43-7.39 (m, 3H), 7.29 (t, J=7.4 Hz, 1H), 7.12 (t, J=5.2 Hz, 1H), 6.69 (d, J=8.4 Hz, 1H), 4.42 (s, 2H), 3.60 (t, J=4.4 Hz, 4H), 3.31 (q, J=5.6 Hz, 2H), 2.57 (t, J=6.4 Hz, 2H), 2.43 (br.s, 4H). [M+H]+: 338.
    • Example 261 7-((2-(Methylamino)ethyl)amino)-4-phenylisoindolin-1-one
  • Figure US20160311772A1-20161027-C00272
  • 1H NMR (400 MHz, DMSO-d6) δ 8.33 (s, 1H), 7.50-7.48 (m, 2H), 7.43-7.39 (m, 3H), 7.30-7.27 (m, 1H), 7.05 (t, J=5.6 Hz, 1H), 6.69 (d, J=8.4 Hz, 1H), 4.41 (s, 2H), 3.26 (q, J=6.0 Hz, 2H), 2.71 (t, J=6.2 Hz, 2H), 2.31 (s, 3H). [M+H]+: 282.
    • Example 262 4-Phenyl-7-((2-(pyrrolidin-1-yl)ethyl)amino)isoindolin-1-one
  • Figure US20160311772A1-20161027-C00273
  • 1H NMR (400 MHz, DMSO-d6) δ 8.31 (s, 1H), 7.50-7.48 (m, 2H), 7.43-7.39 (m, 3H), 7.31-7.27 (m, 1H), 7.04 (t, J=5.6 Hz, 1H), 6.68 (d, J=8.4 Hz, 1H), 4.42 (s, 2H), 3.31 (q, J=6.0 Hz, 4H), 2.67 (t, J=6.4 Hz, 2H), 1.72-1.68 (m, 4H). [M+H]+: 322.
    • Example 263 7-(Benzylamino)-4-phenylisoindolin-1-one
  • Figure US20160311772A1-20161027-C00274
  • 1H NMR (400 MHz, DMSO-d6) δ 8.41 (s, 1H), 7.50-7.46 (m, 2H), 7.45-7.32 (m, 8H), 7.32-7.22 (m, 2H), 6.62 (d, J=8.5 Hz, 1H), 4.50 (d, J=6.2 Hz, 2H), 4.42 (d, J=12.2 Hz, 2H); [M+H]+: 315.
    • Example 264 2-(3-((3-Oxo-7-phenylisoindolin-4-yl)amino)propyl)isoindolin-1,3-dione
  • Figure US20160311772A1-20161027-C00275
  • 1H NMR (400 MHz, CDCl3) δ 7.85 (dd, J=5.4, 3.0 Hz, 2H), 7.71 (dd, J=5.5, 3.0 Hz, 2H), 7.44-7.36 (m, 5H), 7.33-7.27 (m, 1H), 7.00 (br s, 1H), 6.64 (d, J=8.4 Hz, 1H), 5.81 (s, 1H), 4.44 (s, 2H), 3.86 (t, J=6.8 Hz, 2H), 3.35 (t, J=7.0 Hz, 2H), 2.08 (p, J=6.9 Hz, 2H); [M+H]+: 412.
    • Example 265 4-(Pyridin-4-yl)-7-(pyrrolidin-1-yl)isoindolin-1-one
  • Figure US20160311772A1-20161027-C00276
  • 1H NMR (400 MHz, DMSO-d6) δ 8.57 (s, 1H), 8.48 (dd, J=4.4, 1.6 Hz, 2H), 7.39 (dd, J=4.4, 1.6 Hz, 2H), 7.20 (d, J=8.4 Hz, 1H), 6.74 (d, J=8.4 Hz, 1H), 4.62 (s, 2H), 3.47 (t, J=6.4 Hz, 4H), 1.94 (t, J=6.4 Hz, 4H). [M+H]+: 280.
    • Example 266 7-(Dimethylamino)-4-(2-((3-methoxyphenyl)amino)pyrimidin-4-yl)isoindolin-1-one
  • Figure US20160311772A1-20161027-C00277
  • 1H NMR (400 MHz, DMSO-d6) δ 9.47 (s, 1H), 8.48 (d, J=5.6 Hz, 1H), 8.42 (s, 1H), 8.03 (d, J=8.4 Hz, 1H), 7.45 (t, J=2.2 Hz, 1H), 7.34 (d, J=8.4 Hz, 1H), 7.25 (d, J=5.6 Hz, 1H), 7.19 (t, J=8.2 Hz, 1H), 6.95 (d, J=8.4 Hz, 1H), 6.55 (dd, J=8.4, 2.0 Hz, 1H), 4.71 (s, 2H), 3.74 (s, 3H), 3.01 (s, 6H). [M+H]+: 376.
    • Example 267 7-(Dimethylamino)-4-(2-((3-fluorophenyl)amino)pyrimidin-4-yl)isoindolin-1-one
  • Figure US20160311772A1-20161027-C00278
  • 1H NMR (400 MHz, DMSO-d6) δ 9.72 (s, 1H), 8.52 (d, J=5.2 Hz, 1H), 8.44 (s, 1H), 8.03 (d, J=8.8 Hz, 1H), 7.79 (d, J=12.8 Hz, 2H), 7.50 (d, J=8.0 Hz, 1H), 7.35-7.29 (m, 2H), 6.97 (d, J=8.8 Hz, 1H), 6.76 (t, J=8.8 Hz, 1H), 4.71 (s, 2H), 3.01 (s, 6H). [M+H]+: 364.
    • Example 268 7-(Butylamino)-4-(2-((3-methoxyphenyl)amino)pyrimidin-4-yl)isoindolin-1-one
  • Figure US20160311772A1-20161027-C00279
  • 1H NMR (400 MHz, DMSO-d6) δ 9.37 (s, 1H), 8.57 (s, 1H), 8.42 (d, J=5.2 Hz, 1H), 8.04 (d, J=8.8 Hz, 1H), 7.45 (s, 1H), 7.32 (d, J=6.4 Hz, 2H), 7.20 (t, J=6.4 Hz, 1H), 6.72 (d, J=8.8 Hz, 1H), 6.54 (dd, J=8.2, 1.2 Hz, 1H), 4.73 (s, 2H), 3.74 (s, 3H), 3.27 (q, J=6.4 Hz, 2H), 1.59 (qunt, J=7.4 Hz, 2H), 1.40 (sextet, J=7.4 Hz, 2H), 0.93 (t, J=7.2 Hz, 3H). [M+H]+: 403.
    • Example 269 7-(Butyl(methyl)amino)-4-(2-((3-methoxyphenyl)amino) pyrimidin-4-yl)isoindolin-1-one
  • Figure US20160311772A1-20161027-C00280
  • 1H NMR (400 MHz, DMSO-d6) δ 9.46 (s, 1H), 8.47 (d, J=5.6 Hz, 1H), 8.38 (s, 1H), 8.00 (d, J=8.4 Hz, 1H), 7.45 (s, 1H), 7.33 (d, J=8.0 Hz, 1H), 7.24-7.17 (m, 2H), 6.94 (d, J=9.2 Hz, 1H), 6.54 (d, J=8.0 Hz, 1H), 4.70 (s, 2H), 3.74 (s, 3H), 3.50 (t, J=7.6 Hz, 2H), 2.97 (s, 3H), 1.55-1.50 (m, 2H), 1.23-1.18 (m, 2H), 0.86-0.81 (m, 3H). [M+H]+: 418.
    • Example 270 7-(Butyl(methyl)amino)-4-(2-((3-methoxyphenyl)amino) pyrimidin-4-yl)-2-methylisoindolin-1-one
  • Figure US20160311772A1-20161027-C00281
  • 1H NMR (400 MHz, DMSO-d6) δ 9.42 (s, 1H), 8.48 (d, J=5.2 Hz, 1H), 8.01 (d, J=8.8 Hz, 1H), 7.42 (s, 1H), 7.31-7.20 (m, 3H), 6.96 (d, J=8.4 Hz, 1H), 6.58 (d, J=7.6 Hz, 1H), 4.76 (s, 2H), 3.75 (s, 3H), 3.48 (t, J=7.2 Hz, 2H), 3.02 (s, 3H), 2.96 (s, 3H), 1.55-1.50 (m, 2H), 1.23-1.18 (m, 2H), 0.86-0.82 (m, 3H). [M+H]+: 432.
  • Figure US20160311772A1-20161027-C00282
    • Example 271 4-Amino-7-phenylisoindolin-1,3-dione Step 1: Preparation of 4-amino-7-bromoisoindolin-1,3-dione (38)
  • Figure US20160311772A1-20161027-C00283
  • To a solution of 4-aminoisoindolin-1,3-dione (37) (0.5 g, 3.08 mmol) in MeOH (50 mL) was added a mixture of NBS (0.58 g, 3.24 mmol) as three portions at room temperature. Then, the mixture thus obtained was stirred at room temperature for 8 hours, and filtered. The filtrate was concentrated to give the crude product of 4-aminoisoindolin-1,3-dione 38 (0.42 g) as a solid, which was directly used in the next step without further purification.
    • Step 2: Preparation of 4-amino-7-phenylisoindolin-1,3-dione (39)
  • Figure US20160311772A1-20161027-C00284
  • To a stirred suspension solution of 4-amino-7-bromoisoindolin-1,3-dione 38 (200 mg, 0.83 mmol) in ACN (13.8 mL) was added phenylboronic acid (202 mg, 1.66 mmol), Pd(OAc)2 (15 mg, 0.066 mmol), P(o-tol)3 (40 mg, 0.13 mmol) and TEA (1.16 mL) The mixture was degassed with N2 three times, stirred at 90° C. under N2 atmosphere for 12 hours, and then filtered through a Celite pad. The reaction mixture was poured to methanol (15 mL), filtered, washed with water, and dried to give 4-amino-7-phenylisoindolin-1,3-dione 39 (120 mg, 61%).
  • The following compounds of Examples 272 to 275 were obtained by using corresponding starting materials and repeating the procedure of Example 271.
    • Example 272 4-Amino-7-(2-methoxyphenyl)isoindolin-1,3-dione
  • Figure US20160311772A1-20161027-C00285
  • 1H NMR (400 MHz, DMSO-d6) δ 10.75 (br.s, 1H), 7.31 (td, J=7.6, 1.6 Hz, 1H), 7.23 (d, J=8.4 Hz, 1H), 7.17 (dd, J=7.6, 1.6 Hz, 1H), 7.03 (d, J=8.0 Hz, 1H), 6.97-6.92 (m, 2H), 6.42 (s, 2H), 3.66 (s, 3H). [M+H]+: 269.
    • Example 273 4-Amino-7-(2,3-dimethoxyphenyl)isoindolin-1,3-dione
  • Figure US20160311772A1-20161027-C00286
  • 1H NMR (400 MHz, DMSO-d6) δ 10.77 (br.s, 1H), 7.21 (d, J=8.4 Hz, 1H), 7.03 (d, J=4.8 Hz, 2H), 6.96 (d, J=8.4 Hz, 1H), 6.77 (d, J=4.6 Hz, 1H), 6.45 (s, 2H), 3.82 (s, 3H), 3.45 (s, 3H). [M+H]+: 299.
    • Example 274 4-Amino-7-(furan-2-yl)isoindolin-1,3-dione
  • Figure US20160311772A1-20161027-C00287
  • 1H NMR (400 MHz, DMSO-d6) δ 11.02 (br.s, 1H), 7.84 (d, J=8.4 Hz, 1H), 7.75 (d, J=9.6 Hz, 1H), 7.57 (br.s, 1H), 7.06 (d, J=8.4 Hz, 1H), 6.64-6.61 (m, 3H). [M+H]+: 229.
    • Example 275 4-Amino-7-(thiophen-2-yl)isoindolin-1,3-dione
  • Figure US20160311772A1-20161027-C00288
  • 1H NMR (400 MHz, DMSO-d6) δ 10.97 (br.s, 1H), 7.67 (d, J=3.2 Hz, 1H), 7.56 (d, J=5.2 Hz, 1H), 7.54 (s, 1H), 7.10 (t, J=4.2 Hz, 1H), 7.02 (d, J=8.8 Hz, 1H), 6.60 (s, 2H). [M+H]+: 245.
    • Example 276 N-(1,3-dioxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00289
  • To a stirred solution of 4-amino-7-phenylisoindolin-1,3-dione 39 (50 mg, 0.21 mmol) in THF (2.1 mL) was added TEA (0.29 mL, 2.10 mmol) at 0° C., and the mixture was stirred for 10 min. Benzoyl chloride (0.12 mL, 1.05 mmol) was added dropwise to the mixture, which was then stirred at room temperature for 12 hours. TEA (0.29 mL) was added to the crude compound thus obtained in methanol (2.1 mL) The mixture was stirred at 60° C. under N2 atmosphere for 12 hours, and the reaction mixture was filtered. The reaction mixture was poured to ACN (15 mL), filtered, washed with water, and dried to give the title compound 40 (7.3 mg, 10%).
  • 1H NMR (400 MHz, DMSO-d6) δ 11.51 (s, 1H), 10.81 (s, 1H), 8.73 (d, J=8.8 Hz, 1H), 8.00 (d, J=6.8 Hz, 2H), 7.77 (d, J=8.8 Hz, 1H), 7.76-7.58 (m, 5H), 7.48-7.42 (m, 3H). [M+H]+: 343.
  • The following compounds of Examples 277 and 278 were obtained by using corresponding starting materials and repeating the procedure of Example 276.
    • Example 277 N-(7-(2-methoxyphenyl)-1,3-dioxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00290
  • 1H NMR (400 MHz, DMSO-d6) δ 11.40 (s, 1H), 10.67 (s, 1H), 8.67 (d, J=8.4 Hz, 1H), 8.00 (d, J=8.4 Hz, 2H), 7.72-7.62 (m, 4H), 7.41 (t, J=7.8 Hz, 1H), 7.28 (dd, J=7.2, 1.6 Hz, 1H), 7.10 (d, J=8.0 Hz, 1H), 7.02 (d, J=7.4 Hz, 1H), 3.69 (s, 3H). [M+H]+: 373.
    • Example 278 N-(7-(2,3-dimethoxyphenyl)-1,3-dioxoisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00291
  • 1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 10.68 (s, 1H), 8.67 (d, J=8.4 Hz, 1H), 8.00 (d, J=8.4 Hz, 2H), 7.70-7.62 (m, 4H), 7.12-7.10 (m, 2H), 6.85-6.87 (m, 1H), 3.86 (s, 3H), 3.50 (s, 3H). [M+H]+: 403.
    • Example 279 4-Fluoro-N-(3-oxo-7-phenyl-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00292
    Figure US20160311772A1-20161027-C00293
    • Step 1: Preparation of 2-amino-5-bromonicotinonitrile (42)
  • Figure US20160311772A1-20161027-C00294
  • 2-Aminonicotinonitrile (95.0 g, 0.80 mol, 1.0 eq) was dissolved in HOAc (2 L) and then Na2CO3 (93.1 g, 0.88 mol, 1.1 eq) was added. Then Br2 (142.6 g, 0.88 mol, 1.1 eq) in HOAc (2 L) was added dropwise to the mixture. The resulting mixture was stirred at room temperature for 18 hours, which was then poured into ice water (10 L), filtered, washed with water (2 L×2) and dried to give the pure intermediate 42 (150.0 g, 0.75 mol, 94.6%).
  • 1H NMR (400 MHz, DMSO-d6) δ 8.28-8.27 (d, J=2.4 Hz, 1H), 8.15-8.14 (d, J=2.4 Hz, 1H), 7.13 (s, 2H).
    • Step 2: Preparation of 5-bromo-2-(2,5-dimethyl-1H-pyrrol-1-yl) nicotinonitrile (44)
  • Figure US20160311772A1-20161027-C00295
  • To a suspension solution of the intermediate 42 (90.0 g, 0.45 mol, 1.0 eq) in toluene (1.5 L) was added the compound 43 (78.2 g, 0.68 mol, 1.5 eq) and 4-methylbenzenesulfonic acid (2.5 g, 0.01 mol, 0.03 eq). The mixture was heated to 110° C. and stirred for 17 hours to remove water by Dean Stark trap. The mixture was cooled to room temperature, removed of toluene (about 1 L), and then added with EtOAc (2 L) and water (1 L). The mixture was filtered; the aqueous layer was extracted with EtOAc (2 L); the organic phase was washed with brine (3 L) and concentrated to give the crude product, which was purified by flash chromatography (EtOAc:Hexane=1:1) to give the intermediate 44 (110.0 g, 0.39 mol, 87.1%).
  • 1H NMR (400 MHz, DMSO-d6) δ 9.07-9.06 (d, J=2.4 Hz, 1H), 8.96-8.95 (d, J=2.4 Hz, 1H), 5.88 (s, 2H), 2.01 (s, 6H).
    • Step 3: Preparation of 5-bromo-2-(2,5-dimethyl-1H-pyrrol-1-yl) nicotinamide (45)
  • Figure US20160311772A1-20161027-C00296
  • The intermediate 44 (45.0 g, 162.97 mmol, 1.0 eq) was dissolved in DMSO (300 mL) and K2CO3 (67.4 g, 488.90 mmol, 3.0 eq) was added. Then, 30% H2O2 (92.3 g, 814.83 mmol, 5.0 eq) was added thereto dropwise at 40° C., and the resulting mixture was stirred for 0.5 hour. The mixture was added with EtOAc (1 L) and water (2 L). The aqueous layer was extracted with EtOAc (1 L), washed with brine (2 L×2), dried over Na2SO4 and concentrated to give the intermediate 45 (43.2 g, 146.8 mmol, 90.1%).
  • 1H NMR (400 MHz, DMSO-d6) δ 8.81-8.08 (d, J=2.4 Hz, 1H), 8.35-8.34 (d, J=2.4 Hz, 1H), 7.58 (s, 1H), 7.47 (s, 1H), 5.73 (s, 2H), 2.99 (s, 2H), 2.54 (s, 1H), 1.92 (s, 6H).
    • Step 4: Preparation of 7-bromo-4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-hydroxy-1H-pyrrolo[3,4-c]pyridin-3(2H)-one (46)
  • Figure US20160311772A1-20161027-C00297
  • To a solution of LiHMDS (455 mL, 455.00 mmol, 4.0 eq) was added dropwise the intermediate 45 (34.0 g, 115.59 mmol, 1.0 eq) in THF (250 mL) at 0° C. The mixture was stirred for 0.5 hour at the above temperature, then was added with DMF (29.5 g, 404.56 mmol, 3.5 eq) dropwise at 0˜5° C., then heated to room temperature, and stirred for 2 hours. A saturated solution of NH4Cl (400 mL) and EtOAc (1 L) was added into the mixture, and then the aqueous layer was extracted with EtOAc (500 mL×2), washed with brine (1 L), dried over Na2SO4 and concentrated to give the residue, which was purified by chromatography (EtOAc:Hexane=1:1) to give the intermediate 46 (13.0 g, 40.3 mmol, 34.8%) as a yellow solid.
  • 1H NMR (400 MHz, DMSO-d6) δ 9.31 (s, 1H), δ 8.89 (s, 1H), 6.70-6.67 (d, J=9.7 Hz, 1H), 5.91-5.90 (d, J=9.8 Hz, 1H), 5.77 (s, 2H), 1.95 (s, 3H), 1.90 (s, 3H).
    • Step 5: Preparation of 4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-hydroxy-7-phenyl-1H-pyrrolo[3,4-c]pyridin-3(2H)-one (47)
  • Figure US20160311772A1-20161027-C00298
  • A suspension solution of intermediate 46 (14.2 g, 44.08 mmol, 1.0 eq), phenylboronic acid (8.06 g, 66.12 mmol, 1.5 eq), and Na2CO3 (9.34 g, 88.15 mmol, 2.0 eq) in DME (450 mL) and water (100 mL) was purged with nitrogen, treated with Pd(PPh3)4 (5.09 g, 4.41 mmol, 0.1 eq), then stirred at 70° C. for 15 hours. The resulting reaction mixture was cooled to room temperature, extracted with EtOAc (1 L×2), washed with brine, dried and concentrated to give the crude product, which was purified by chromatography (EtOAc:Hexane=1:1) to give the intermediate 47 (8.2 g, 25.6 mmol, 58.2%).
  • 1H NMR (400 MHz, DMSO-d6) δ 9.17 (s, 1H), 8.78 (s, 1H), 7.81-7.79 (m, 2H), 7.55-7.45 (m, 3H), 6.39-6.32 (m, 2H), 5.78 (s, 2H), 2.00 (s, 3H), 1.94 (s, 3H).
    • Step 6: Preparation of 4-amino-1-hydroxy-7-phenyl-1H-pyrrolo[3,4-c]pyridin-3(2H)-one (48)
  • Figure US20160311772A1-20161027-C00299
  • To a suspension solution of the intermediate 47 (11.5 g, 36.01 mmol, 1.0 eq) in EtOH (190 mL) was added a solution of NH2OH.HCl (13.7 g, 198.05 mmol, 5.5 eq) and KOH (7.8 g, 126.03 mmol, 3.5 eq, in 70 mL water). The mixture was stirred at 80° C. for 20 hours. The resulting reaction mixture was cooled to room temperature, and added with Na2CO3 (pH about 7˜8), and removed of EtOH. The mixture was then added with EtOAc (300 mL) and water (300 mL), filtered, and then the solid thus obtained was washed with EtOAc and dried to give the intermediate 48 (4.2 g, 17.4 mmol, 48.3%, HPLC: 90%).
  • 1H NMR (400 MHz, DMSO-d6) δ 8.77 (s, 1H), 8.18 (s, 1H), 7.63-7.61 (d, J=7.3 Hz, 2H), 7.43-7.37 (t, J=7.4 Hz, 2H), 7.33-7.30 (m, 1H), 6.68 (s, 2H), 6.24-6.22 (m, 1H), 6.14-6.12 (m, 1H).
    • Step 7: Preparation of 4-amino-7-phenyl-1H-pyrrolo[3,4-c]pyridin-3(2H)-one (49)
  • Figure US20160311772A1-20161027-C00300
  • To a solution of intermediate 48 (4.9 g, 20.31 mmol, 1.0 eq) in TFA (90 mL) was added Et3SiH (23.6 g, 203.11 mmol, 10 eq). The mixture was stirred at 50° C. for 17 hours. The reaction mixture was concentrated, added with DCM (150 mL) and water (150 mL), adjusted to the pH of about 7 with NaHCO3, and filtered. The aqueous layer was extracted with DCM (200 mL×2), washed with brine, and then concentrated to give the crude product, which was purified by chromatography (DCM: MeOH=150:1) to give the pure compound 49 (1.37 g, 6.08 mmol, 29.9%) as a yellow solid.
  • 1H NMR (400 MHz, DMSO-d6) δ 8.55 (s, 1H), 8.20 (s, 1H), 7.56-7.54 (d, J=7.3 Hz, 2H), 7.47-7.43 (t, J=7.4 Hz, 1H), 7.36-7.32 (t, J=7.3 Hz, 1H), 6.75 (s, 2H), 4.52 (s, 2H).
    • Step 8: Preparation of 4-fluoro-N-(3-oxo-7-phenyl-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yl)benzamide (50)
  • Figure US20160311772A1-20161027-C00301
  • To a suspension solution of the compound 49 (800 mg, 3.55 mmol, 1.0 eq) in pyridine (20 mL) was added 4-fluorobenzoyl chloride (619 mg, 3.91 mmol, 1.1 eq).
  • The mixture was stirred at 100° C. for 2 hours. The reaction mixture was cooled to room temperature, added with EtOAc (50 mL) and water (50 mL), and filtered. The aqueous layer was extracted with EtOAc (50 mL×5), washed with brine, and concentrated to give the crude product, which was purified by chromatography (DCM: MeOH=50:1) to give the title compound 50 (42 mg, 0.12 mmol, 3.4%) as a yellow solid.
  • 1H NMR (400 MHz, DMSO-d6) δ 8.36 (s, 1H), 7.73-7.70 (m, 2H), 7.59-7.58 (m, 2H), 7.53-7.49 (t, J=7.5 Hz, 2H), 7.41-7.38 (m, 1H), 7.30-7.28 (m, 2H), 5.08 (s, 2H).
    • Example 280 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00302
    • Step 1: Preparation of N-(7-bromo-3-oxoisoindolin-4-yl)-4-fluorobenzamide (51)
  • Figure US20160311772A1-20161027-C00303
  • To a suspension solution of 7-amino-4-bromoisoindolin-1-one 6 (33.2 g, 0.146 mol) in THF (1.7 L) was added NMM (29.5 g, 0.292 mol) dropwise at 0° C. over 5 min, and then 4-fluorobenzoyl chloride (34.7 g, 0.219 mol) was added dropwise over 20 min at 0° C. The resulting reaction mixture was stirred at room temperature overnight, and then poured into water (2 L). THF was removed by evaporating the mixture in vacuo, and the residue solid thus obtained was washed with EtOAc (3×300 mL) and filtered. The filter cake was dried to give the title product 51 (40 g).
  • 1H NMR (400 MHz, DMSO-d6) δ 11.39 (s, 1H), 9.20 (s, 1H), 8.41-8.38 (d, J=8.8 Hz, 1H), 8.01 (s, 2H), 7.81-7.79 (d, J=8.6 Hz, 1H), 7.48-7.44 (t, J=8.3 Hz, 2H), 4.37 (s, 2H).
    • Step 2: Preparation of N-(7-bromo-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide (53)
  • Figure US20160311772A1-20161027-C00304
  • A mixture of N-(7-bromo-3-oxoisoindolin-4-yl)-4-fluorobenzamide (600 mg, 1.72 mmol) in 1-(3-aminopropyl)pyrrolidine (1.1 mL, 8.6 mmol) was stirred for 12 hours at 160° C., and then cooled to room temperature. After CH3OH was poured into the mixture, the mixture was stirred for 1 hour. The obtained solid was washed with CH3OH to give the title compound (380 mg, 48%) as a pale yellow solid.
  • 1H NMR (400 MHz, DMSO-d6) δ 11.18 (br s, 1H), 9.13 (br s, 1H), 8.42 (d, J=8.8 Hz, 1H), 7.74 (d, J=8.8 Hz, 1H), 7.70 (d, J=8.8 Hz, 2H), 6.66 (d, J=8.8 Hz, 2H), 6.56 (t, J=5.4 Hz, 1H), 4.35 (s, 2H), 3.16-3.11 (m, 2H), 2.50-2.48 (m, 2H), 2.43-2.41 (m, 4H), 1.74-1.71 (m, 2H), 1.70-1.67 (m, 4H); [M+H]+: 457.
    • Step 3: Preparation of N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide (54)
  • Figure US20160311772A1-20161027-C00305
  • A mixture of the compound 53 (75 mg, 0.16 mmol), (2,3-dimethoxyphenyl)boronic acid (60 mg, 0.33 mmol), Pd(PPh3)4 (19 mg, 0.02 mmol) and Na2CO3 (70 mg, 0.66 mmol) in DME/H2O (2/0.5 mL) was stirred for 12 hours at 100° C. The resulting mixture was diluted with CH2Cl2 and washed with 1M Na2CO3 (aq.). The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The crude product thus obtained was purified by silica-gel column chromatography (Biotage flash purification system, CH2Cl2/CH3OH, KP-Sil) to provide the title compound 54 (9 mg, 11%) as a white solid.
  • 1H NMR (400 MHz, DMSO-d6) δ 11.40 (br s, 1H), 8.92 (br s, 1H), 8.52 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.50 (d, J=8.4 Hz, 1H), 7.17-7.09 (m, 2H), 6.94 (dd, J=7.4, 1.8 Hz, 1H), 6.68 (d, J=8.8 Hz, 2H), 6.54 (t, J=5.0 Hz, 1H), 4.29 (s, 2H), 3.85 (s, 3H), 3.44 (s, 3H), 3.17-3.12 (m, 2H), 2.47-2.43 (m, 4H), 1.77-1.74 (m, 2H), 1.712-1.68 (m, 4H); [M+H]+: 515.
  • The following compounds of Examples 281 to 387 were obtained by using corresponding starting materials and repeating the procedure of Example 280.
    • Example 281 N-(7-bromo-3-oxoisoindolin-4-yl)-4-((2-(dimethylamino)ethyl) amino)benzamide
  • Figure US20160311772A1-20161027-C00306
  • 1H NMR (400 MHz, DMSO-d6) δ 11.19 (br s, 1H), 9.13 (br s, 1H), 8.42 (d, J=8.8 Hz, 1H), 7.74 (d, J=8.8 Hz, 1H), 7.70 (d, J=8.4 Hz, 2H), 6.71 (d, J=8.8 Hz, 2H), 6.35 (t, J=5.2 Hz, 1H), 4.35 (s, 2H), 3.20-3.16 (m, 2H), 2.48-2.44 (m, 2H), 2.20 (s, 6H); [M+H]+: 417.
    • Example 282 N-(7-bromo-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl) propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00307
  • 1H NMR (400 MHz, DMSO-d6) δ 11.18 (br s, 1H), 9.14 (br s, 1H), 8.42 (d, J=8.8 Hz, 1H), 7.74 (d, J=8.8 Hz, 1H), 7.70 (d, J=8.8 Hz, 2H), 6.66 (d, J=8.8 Hz, 2H), 6.60 (t, J=5.2 Hz, 1H), 4.34 (s, 2H), 3.14-3.09 (m, 2H), 2.34-2.30 (m, 6H), 1.73-1.65 (m, 2H), 1.53-1.47 (m, 4H), 1.39-1.37 (m, 2H); [M+H]+: 471.
    • Example 283 N-(7-bromo-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl) amino)benzamide
  • Figure US20160311772A1-20161027-C00308
  • 1H NMR (400 MHz, DMSO-d6) δ 11.19 (s, 1H), 9.15 (s, 1H), 8.42 (d, J=8.8 Hz, 1H), 7.74 (d, J=8.8 Hz, 1H), 7.69 (d, J=8.4 Hz, 2H), 6.69 (d, J=8.8 Hz, 2H), 6.45 (t, J=5.0 Hz, 1H), 4.35 (s, 2H), 3.21 (q, J=6.4 Hz, 2H), 2.61 (t, J=6.6 Hz, 2H), 2.49-2.45 (m, 4H), 1.72-1.68 (m, 4H). [M+H]+: 444.
    • Example 284 N-(7-bromo-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl) amino)benzamide
  • Figure US20160311772A1-20161027-C00309
  • 1H NMR (400 MHz, DMSO-d6) δ 11.19 (s, 1H), 9.13 (s, 1H), 8.42 (d, J=8.8 Hz, 1H), 7.74 (d, J=8.8 Hz, 1H), 7.69 (d, J=8.8 Hz, 2H), 6.69 (d, J=8.8 Hz, 2H), 6.35 (t, J=5.4 Hz, 1H), 4.35 (s, 2H), 3.20 (q, J=6.0 Hz, 2H), 2.46 (t, J=5.8 Hz, 2H), 2.42-2.36 (m, 4H), 1.53-1.48 (m, 4H), 1.39-1.36 (m, 2H). [M+H]+: 458.
    • Example 285 4-((2-(azepan-1-yl)ethyl)amino)-N-(7-bromo-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00310
  • 1H NMR (400 MHz, DMSO-d6) δ 11.19 (s, 1H), 9.13 (s, 1H), 8.42 (d, J=8.8 Hz, 1H), 7.74 (d, J=8.8 Hz, 1H), 7.70 (d, J=8.8 Hz, 2H), 6.69 (d, J=8.8 Hz, 2H), 6.31 (t, J=5.4 Hz, 1H), 4.35 (s, 2H), 3.17 (q, J=6.4 Hz, 2H), 2.68-2.63 (m, 6H), 1.59-1.53 (m, 8H). [M+H]+: 472.
    • Example 286 N-(7-bromo-3-oxoisoindolin-4-yl)-4-((3-(dimethylamino) propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00311
  • 1H NMR (400 MHz, DMSO-d6) δ 11.18 (s, 1H), 9.13 (s, 1H), 8.42 (d, J=8.8 Hz, 1H), 7.74 (d, J=8.4 Hz, 1H), 7.69 (d, J=8.8 Hz, 2H), 6.66 (d, J=8.8 Hz, 2H), 6.54 (t, J=5.6 Hz, 1H), 4.35 (s, 2H), 3.11 (q, J=6.4 Hz, 2H), 2.30-2.27 (m, 2H), 2.14 (s, 6H), 1.68 (quint, J=6.8 Hz, 2H). [M+H]+: 432.
    • Example 287 N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl) ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00312
  • 1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 9.14 (s, 1H), 8.54 (d, J=8.6 Hz, 1H), 7.94 (d, J=8.6 Hz, 1H), 7.82 (d, J=1.3 Hz, 1H), 7.75 (d, J=8.7 Hz, 2H), 6.85 (d, J=3.4 Hz, 1H), 6.76 (d, J=8.6 Hz, 2H), 6.66 (dd, J=3.3, 1.8 Hz, 2H), 4.63 (s, 2H), 3.46-3.35 (m, 3H), 1.92-1.83 (m, 5H); MS (ESI) m/z 431 (M+H)+.
    • Example 288 N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((2-methoxyethyl) amino)benzamide
  • Figure US20160311772A1-20161027-C00313
  • 1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 9.13 (s, 1H), 8.54 (d, J=8.6 Hz, 1H), 7.93 (d, J=8.6 Hz, 1H), 7.81 (d, J=1.3 Hz, 1H), 7.72 (d, J=8.7 Hz, 2H), 6.85 (d, J=3.4 Hz, 1H), 6.72 (d, J=8.8 Hz, 2H), 6.66 (dd, J=3.4, 1.8 Hz, 1H), 6.55 (t, J=5.5 Hz, 1H), 4.63 (s, 2H), 3.51 (t, J=5.5 Hz, 2H), 3.32-3.25 (m, 5H); MS (ESI) m/z 392 (M+H)+.
    • Example 289 N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl) ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00314
  • 1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 9.13 (s, 1H), 8.54 (d, J=8.6 Hz, 1H), 7.94 (d, J=8.6 Hz, 1H), 7.82 (d, J=1.4 Hz, 1H), 7.77 (d, J=8.7 Hz, 2H), 6.85 (d, J=3.4 Hz, 1H), 6.76 (d, J=8.6 Hz, 2H), 6.67 (dd, J=3.4, 1.8 Hz, 1H), 6.58 (br s, 1H), 4.64 (s, 2H), 3.46-3.35 (m, 3H), 1.87-1.53 (m, 8H); MS (ESI) m/z 445 (M+H)+.
    • Example 290 N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((2-morpholinoethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00315
  • 1H NMR (400 MHz, DMSO-d6) δ 11.46 (s, 1H), 9.12 (s, 1H), 8.54 (d, J=8.6 Hz, 1H), 7.94 (d, J=8.6 Hz, 1H), 7.82 (d, J=1.4 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 6.85 (d, J=3.4 Hz, 1H), 6.71 (d, J=8.8 Hz, 2H), 6.66 (dd, J=3.3, 1.8 Hz, 1H), 6.38 (t, J=5.3 Hz, 1H), 4.63 (s, 2H), 3.59 (t, J=4.5 Hz, 4H), 3.27-3.21 (m, 2H), 2.51-2.30 (m, 6H); MS (ESI) m/z 447 (M+H)+.
    • Example 291 4-((2-(Dimethylamino)ethyl)amino)-N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00316
  • 1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 9.13 (s, 1H), 8.54 (d, J=8.6 Hz, 1H), 7.94 (d, J=8.6 Hz, 1H), 7.82 (d, J=1.4 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 6.85 (d, J=3.4 Hz, 1H), 6.71 (d, J=8.8 Hz, 2H), 6.66 (dd, J=3.3, 1.8 Hz, 1H), 6.38 (t, J=5.3 Hz, 1H), 4.63 (s, 2H), 3.41-3.30 (m, 2H), 2.97-2.85 (m, 2H), 2.56 (s, 6H); MS (ESI) m/z 405 (M+H)+.
    • Example 292 N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((2-hydroxyethyl) amino)benzamide
  • Figure US20160311772A1-20161027-C00317
  • 1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 9.12 (s, 1H), 8.54 (d, J=8.6 Hz, 1H), 7.93 (d, J=8.6 Hz, 1H), 7.81 (s, 1H), 7.72 (d, J=8.4 Hz, 2H), 6.84 (d, J=2.6 Hz, 1H), 6.71 (d, J=8.4 Hz, 2H), 6.66 (s, 1H), 6.49 (t, J=4.9 Hz, 1H), 4.77 (t, J=5.1 Hz, 1H), 4.63 (s, 2H), 3.61-3.50 (m, 2H), 3.19-3.13 (m, 2H); MS (ESI) m/z 378 (M+H)+.
    • Example 293 4-((2-(Azepan-1-yl)ethyl)amino)-N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00318
  • 1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 9.13 (s, 1H), 8.54 (d, J=8.6 Hz, 1H), 7.93 (d, J=8.6 Hz, 1H), 7.82 (s, 1H), 7.72 (d, J=8.3 Hz, 2H), 6.84 (d, J=2.6 Hz, 1H), 6.70 (d, J=8.3 Hz, 2H), 6.66 (s, 1H), 6.31 (t, J=5.1 Hz, 1H), 4.63 (s, 2H), 3.23-3.13 (m, 2H), 2.71-2.60 (m, 6H), 1.71-1.45 (m, 9H); MS (ESI) m/z 459 (M+H)+.
    • Example 294 N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((2-(4-methylpiperazin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00319
  • 1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 9.12 (s, 1H), 8.53 (d, J=8.6 Hz, 1H), 7.92 (d, J=8.6 Hz, 1H), 7.81 (d, J=1.4 Hz, 1H), 7.71 (d, J=8.7 Hz, 2H), 6.83 (d, J=3.3 Hz, 1H), 6.69 (d, J=8.7 Hz, 2H), 6.65 (dd, J=3.2, 1.8 Hz, 1H), 6.39 (t, J=5.3 Hz, 1H), 4.62 (s, 2H), 3.20 (q, J=6.2 Hz, 2H), 2.49-2.07 (m, 10H), 2.13 (s, 3H); MS (ESI) m/z 460 (M+H)+.
    • Example 295 N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((3-(4-methyl piperazin-1-yl)propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00320
  • 1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 9.12 (s, 1H), 8.54 (d, J=8.6 Hz, 1H), 7.93 (d, J=8.6 Hz, 1H), 7.82 (d, J=1.5 Hz, 1H), 7.72 (d, J=8.7 Hz, 2H), 6.84 (d, J=3.4 Hz, 1H), 6.68-6.66 (m, 3H), 6.56 (t, J=8.7 Hz, 1H), 4.63 (s, 2H), 3.12 (q, J=6.2 Hz, 2H), 2.38-2.34 (m, 7H), 2.15 (s, 4H), 1.70 (quint, J=6.9 Hz, 3H); [M+H]+: 459.
    • Example 296 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-morpholinopropyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00321
  • 1H NMR (400 MHz, DMSO-d6) δ 11.40 (br s, 1H), 8.89 (br s, 1H), 8.52 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.50 (d, J=8.4 Hz, 1H), 7.17-7.09 (m, 2H), 6.94 (dd, J=7.4, 1.8 Hz, 1H), 6.68 (d, J=8.8 Hz, 2H), 6.53 (t, J=5.4 Hz, 1H), 4.29 (s, 2H), 3.85 (s, 3H), 3.59 (t, J=4.4 Hz, 2H), 3.44 (s, 3H), 3.17-3.12 (m, 2H), 2.50-2.48 (m, 2H), 2.39-2.35 (m, 6H), 1.72 (quint, J=6.8 Hz, 2H); [M+H]+: 531.
    • Example 297 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-morpholinoethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00322
  • 1H NMR (400 MHz, DMSO-d6) δ 11.41 (br s, 1H), 8.90 (br s, 1H), 8.52 (d, J=8.8 Hz, 1H), 7.74 (d, J=8.8 Hz, 2H), 7.50 (d, J=8.4 Hz, 1H), 7.17-7.09 (m, 2H), 6.94 (dd, J=7.4, 1.8 Hz, 1H), 6.72 (d, J=8.8 Hz, 2H), 6.36 (t, J=5.4 Hz, 1H), 4.29 (s, 2H), 3.85 (s, 3H), 3.60 (t, J=4.6 Hz, 4H), 3.44 (s, 3H), 3.24 (q, J=6.4 Hz, 2H), 2.50-2.48 (m, 2H), 2.44-2.43 (m, 4H); [M+H]+: 517.
    • Example 298 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00323
  • 1H NMR (400 MHz, DMSO-d6) δ 11.41 (br s, 1H), 8.90 (br s, 1H), 8.52 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.50 (d, J=8.4 Hz, 1H), 7.17-7.09 (m, 2H), 6.94 (dd, J=7.2, 1.6 Hz, 1H), 6.71 (d, J=8.8 Hz, 2H), 6.32 (t, J=5.2 Hz, 1H), 4.29 (s, 2H), 3.85 (s, 3H), 3.44 (s, 3H), 3.21 (q, J=6.4 Hz, 2H), 2.50-2.48 (m, 2H), 2.42-2.40 (m, 4H), 1.55-1.48 (m, 4H), 1.41-1.39 (m, 2H); [M+H]+: 515.
    • Example 299 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00324
  • 1H NMR (400 MHz, DMSO-d6) δ 11.40 (br s, 1H), 8.90 (br s, 1H), 8.52 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.50 (d, J=8.4 Hz, 1H), 7.17-7.09 (m, 2H), 6.94 (dd, J=7.4, 1.8 Hz, 1H), 6.71 (d, J=8.8 Hz, 2H), 6.40 (t, J=5.4 Hz, 1H), 4.29 (s, 2H), 3.85 (s, 3H), 3.44 (s, 3H), 3.22 (q, J=5.6 Hz, 2H), 2.63 (t, J=6.8 Hz, 2H), 2.50-2.48 (m, 4H), 1.71-1.68 (m, 4H); [M+H]+: 501.
    • Example 300 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-methoxyethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00325
  • 1H NMR (400 MHz, DMSO-d6) δ 11.41 (br s, 1H), 8.90 (br s, 1H), 8.52 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.4 Hz, 2H), 7.50 (d, J=8.4 Hz, 1H), 7.17-7.09 (m, 2H), 6.94 (dd, J=7.2, 1.6 Hz, 1H), 6.73 (d, J=8.8 Hz, 2H), 6.53 (t, J=5.6 Hz, 1H), 4.29 (s, 2H), 3.85 (s, 3H), 3.52-3.49 (m, 2H), 3.44 (s, 3H), 3.30-3.28 (m, 2H), 3.29 (s, 3H); [M+H]+: 462.
    • Example 301 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(dimethylamino)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00326
  • 1H NMR (400 MHz, DMSO-d6) δ 11.41 (br s, 1H), 8.91 (br s, 1H), 8.52 (d, J=8.8 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.50 (d, J=8.4 Hz, 1H), 7.17-7.09 (m, 2H), 6.94 (dd, J=7.4, 1.8 Hz, 1H), 6.72 (d, J=8.8 Hz, 2H), 6.33 (t, J=5.6 Hz, 1H), 4.29 (s, 2H), 3.85 (s, 3H), 3.44 (s, 3H), 3.22-3.17 (m, 2H), 2.50-2.48 (m, 2H), 2.21 (s, 6H); [M+H]+: 475.
    • Example 302 N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00327
  • 1H NMR (400 MHz, DMSO-d6) δ 11.40 (br s, 1H), 8.89 (br s, 1H), 8.50 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.47 (d, J=8.4 Hz, 1H), 7.42-7.37 (m, 1H), 7.30 (dd, J=7.2, 1.6 Hz, 1H), 7.13 (d, J=8.0 Hz, 1H), 7.04 (t, J=7.4 Hz, 1H), 6.68 (d, J=8.8 Hz, 2H), 6.53 (t, J=5.4 Hz, 1H), 4.24 (s, 2H), 3.76 (s, 3H), 3.14 (q, J=5.6 Hz, 2H), 2.50-2.48 (m, 2H), 2.47-2.43 (m, 4H), 1.75-1.69 (s, 6H); [M+H]+: 485.
    • Example 303 N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide hydrochloride
  • Figure US20160311772A1-20161027-C00328
  • 1H NMR (400 MHz, DMSO-d6) δ 11.45 (br s, 1H), 10.14 (br s, 1H), 8.92 (br s, 1H), 8.50 (d, J=8.4 Hz, 1H), 7.80 (d, J=8.8 Hz, 2H), 7.48 (d, J=8.4 Hz, 1H), 7.42-7.38 (m, 1H), 7.31 (dd, J=7.2, 1.6 Hz, 1H), 7.14 (d, J=8.0 Hz, 1H), 7.04 (t, J=7.4 Hz, 1H), 6.80 (d, J=8.8 Hz, 2H), 6.77-6.76 (m, 1H), 4.25 (s, 2H), 3.76 (s, 3H), 3.61-3.58 (m, 2H), 3.56-3.51 (m, 2H), 3.33-3.31 (m, 2H), 3.07-3.00 (m, 2H), 2.05-1.96 (m, 2H), 1.92-1.86 (m, 2H); [M+H]+: 471 (free form).
    • Example 304 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide hydrochloride
  • Figure US20160311772A1-20161027-C00329
  • 1H NMR (400 MHz, DMSO-d6) δ 11.46 (br s, 1H), 10.29 (br s, 1H), 8.95 (br s, 1H), 8.51 (d, J=8.4 Hz, 1H), 7.79 (d, J=8.8 Hz, 2H), 7.51 (d, J=8.4 Hz, 1H), 7.17-7.09 (m, 2H), 6.94 (dd, J=7.4, 1.8 Hz, 1H), 6.81-6.76 (m, 3H), 4.29 (s, 2H), 3.85 (s, 3H), 3.62-3.58 (m, 2H), 3.56-3.52 (m, 2H), 3.33-3.32 (m, 2H), 3.05-3.03 (m, 2H), 2.02-2.00 (m, 2H), 1.88-1.87 (m, 2H); [M+H]+: 501 (free form).
    • Example 305 4-((2-(Dimethylamino)ethyl)amino)-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00330
  • 1H NMR (400 MHz, DMSO-d6) δ 11.41 (br s, 1H), 8.91 (br s, 1H), 8.50 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.4 Hz, 2H), 7.47 (d, J=8.4 Hz, 1H), 7.42-7.39 (m, 1H), 7.38 (dd, J=7.2, 1.6 Hz, 1H), 7.31 (dd, J=7.4, 1.4 Hz, 1H), 7.14 (d, J=8.4 Hz, 1H), 7.04 (t, J=7.4 Hz, 1H), 6.72 (d, J=8.8 Hz, 2H), 6.34 (t, J=5.2 Hz, 1H), 4.25 (s, 2H), 3.76 (s, 3H), 3.19-3.18 (m, 2H), 2.48-2.45 (m, 2H), 2.20 (s, 6H); [M+H]+: 445.
    • Example 306 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-(dimethylamino)propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00331
  • 1H NMR (400 MHz, DMSO-d6) δ 11.40 (br s, 1H), 8.92 (br s, 1H), 8.52 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.50 (d, J=8.4 Hz, 1H), 7.17-7.09 (m, 2H), 6.94 (dd, J=7.4, 1.8 Hz, 1H), 6.68 (d, J=8.8 Hz, 2H), 6.53 (t, J=5.6 Hz, 1H), 4.29 (s, 2H), 3.85 (s, 3H), 3.44 (s, 3H), 3.16-3.10 (m, 2H), 2.30-2.28 (m, 2H), 2.15 (s, 6H), 1.72-1.65 (m, 2H); [M+H]+: 489.
    • Example 307 N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00332
  • 1H NMR (400 MHz, DMSO-d6) δ 11.40 (br s, 1H), 8.91 (br s, 1H), 8.50 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.47 (d, J=8.4 Hz, 1H), 7.42-7.37 (m, 1H), 7.31 (d, J=7.6 Hz, 1H), 7.13 (d, J=8.4 Hz, 1H), 7.04 (t, J=7.6 Hz, 1H), 6.68 (d, J=8.8 Hz, 2H), 6.58 (t, J=5.2 Hz, 1H), 4.25 (s, 2H), 3.76 (s, 3H), 3.16-3.12 (m, 2H), 2.35-2.31 (m, 6H), 1.72-1.68 (m, 2H), 1.52-1.49 (m, 4H), 1.39-1.37 (m, 2H); [M+H]+: 499.
    • Example 308 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00333
  • 1H NMR (400 MHz, DMSO-d6) δ 11.40 (br s, 1H), 8.91 (br s, 1H), 8.50 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.4 Hz, 2H), 7.50 (d, J=8.4 Hz, 1H), 7.17-7.09 (m, 2H), 6.94 (d, J=6.4 Hz, 1H), 6.67 (d, J=8.4 Hz, 2H), 6.57 (t, J=5.2 Hz, 1H), 4.29 (s, 2H), 3.85 (s, 3H), 3.44 (s, 3H), 3.17-3.11 (m, 2H), 2.35-2.31 (m, 6H), 1.72-1.68 (m, 2H), 1.52-1.48 (m, 4H), 1.39-1.37 (m, 2H); [M+H]+: 529.
    • Example 309 2-Methyl-N-(3-oxo-7-phenylisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00334
  • 1H NMR (400 MHz, DMSO-d6) δ 11.05 (br s, 1H), 8.98 (br s, 1H), 8.55 (d, J=8.4 Hz, 1H), 7.66 (d, J=8.4 Hz, 1H), 7.61 (d, J=7.6 Hz, 2H), 7.50-7.44 (m, 3H), 7.41-7.39 (m, 1H), 6.53-6.49 (m, 2H), 6.13-6.11 (m, 1H), 4.57 (s, 2H), 3.20-3.18 (m, 2H), 2.61-2.59 (m, 2H), 2.50-2.49 (m, 4H), 2.44 (s, 3H), 1.70-1.68 (m, 4H); [M+H]+: 455.
    • Example 310 4-((3-Methoxypropyl)amino)-N-(7-(2-methoxypyridin-3-yl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00335
  • 1H NMR (400 MHz, DMSO-d6) δ 11.43 (br s, 1H), 8.95 (br s, 1H), 8.52 (d, J=8.4 Hz, 1H), 8.23 (dd, J=5.0, 1.8 Hz, 1H), 7.79 (dd, J=7.2, 1.6 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.54 (d, J=8.4 Hz, 1H), 7.11 (m, 1H), 6.68 (d, J=8.8 Hz, 2H), 6.52 (t, J=5.2 Hz, 1H), 4.31 (s, 2H), 3.88 (s, 3H), 3.44-3.40 (m, 2H), 3.26 (s, 3H), 3.18-3.13 (m, 2H), 1.83-1.76 (m, 2H); [M+H]+: 447.
    • Example 311 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-hydroxyethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00336
  • 1H NMR (400 MHz, DMSO-d6) δ 11.41 (br s, 1H), 8.91 (br s, 1H), 8.52 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.4 Hz, 2H), 7.50 (d, J=8.4 Hz, 1H), 7.17-7.09 (m, 2H), 6.94 (dd, J=7.2, 1.6 Hz, 1H), 6.71 (d, J=8.8 Hz, 2H), 6.48 (t, J=5.6 Hz, 1H), 4.77 (t, J=5.4 Hz, 1H), 4.29 (s, 2H), 3.85 (s, 3H), 3.59-3.57 (m, 2H), 3.44 (s, 3H), 3.20-3.18 (m, 2H); [M+H]+: 448.
    • Example 312 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-morpholinobenzamide
  • Figure US20160311772A1-20161027-C00337
  • 1H NMR (400 MHz, DMSO-d6) δ 11.52 (br s, 1H), 8.94 (br s, 1H), 8.52 (d, J=8.4 Hz, 1H), 7.85 (d, J=9.2 Hz, 2H), 7.52 (d, J=8.4 Hz, 1H), 7.17-7.09 (m, 4H), 6.94 (dd, J=7.4, 1.8 Hz, 1H), 4.30 (s, 2H), 3.85 (s, 3H), 3.77-3.74 (m, 4H), 3.45 (s, 3H), 3.33-3.28 (m, 2H); [M+H]+: 474.
    • Example 313 N-(7-(3-fluoro-2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00338
  • 1H NMR (400 MHz, DMSO-d6) δ 11.42 (br s, 1H), 8.96 (br s, 1H), 8.52 (d, J=8.4 Hz, 1H), 7.74 (d, J=8.8 Hz, 2H), 7.54 (d, J=8.4 Hz, 1H), 7.36-7.30 (m, 1H), 7.24-7.16 (m, 2H), 6.71 (d, J=8.8 Hz, 2H), 6.42 (t, J=5.4 Hz, 1H), 4.32 (s, 2H), 3.60 (d, J=1.2 Hz, 3H), 3.25-3.20 (m, 2H), 2.65-2.60 (m, 2H), 2.51-2.50 (m, 2H), 1.72-1.69 (m, 4H); [M+H]+: 489.
    • Example 314 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(4-methylpiperazin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00339
  • 1H NMR (400 MHz, DMSO-d6) δ 11.41 (br s, 1H), 8.92 (br s, 1H), 8.52 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.50 (d, J=8.4 Hz, 1H), 7.17-7.09 (m, 2H), 6.94 (dd, J=7.4, 1.8 Hz, 1H), 6.71 (d, J=8.8 Hz, 2H), 6.34 (t, J=5.4 Hz, 1H), 4.29 (s, 2H), 3.85 (s, 3H), 3.44 (s, 3H), 3.22-3.19 (m, 2H), 2.50-2.48 (m, 4H), 2.35-2.27 (m, 6H), 2.15 (s, 3H); [M+H]+: 530.
    • Example 315 4-((2-Aminoethyl)amino)-N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00340
  • 1H NMR (400 MHz, DMSO-d6) δ 11.41 (br s, 1H), 8.91 (br s, 1H), 8.52 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.50 (d, J=8.4 Hz, 1H), 7.17-7.09 (m, 2H), 6.94 (dd, J=7.4, 1.8 Hz, 1H), 6.70 (d, J=9.2 Hz, 2H), 6.49 (t, J=5.6 Hz, 1H), 4.29 (s, 2H), 3.85 (s, 3H), 3.44 (s, 3H), 3.12-3.07 (m, 2H), 2.75-2.72 (m, 2H); [M+H]+: 447.
    • Example 316 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-(4-methylpiperazin-1-yl)propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00341
  • 1H NMR (400 MHz, DMSO-d6) δ 11.40 (br s, 1H), 8.90 (br s, 1H), 8.52 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.50 (d, J=8.4 Hz, 1H), 7.17-7.09 (m, 2H), 6.94 (d, J=8.8 Hz, 1H), 6.71 (d, J=8.8 Hz, 2H), 6.54 (t, J=5.4 Hz, 1H), 4.29 (s, 2H), 3.85 (s, 3H), 3.44 (s, 3H), 3.15-3.10 (m, 2H), 2.40-2.32 (m, 10H), 2.16 (s, 3H), 1.74-1.66 (m, 2H); [M+H]+: 544.
    • Example 317 N-(3-oxo-7-phenylisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl) ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00342
  • 1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 9.00 (s, 1H), 8.57 (d, J=8.4 Hz, 1H), 7.74 (d, J=8.5 Hz, 2H), 7.67 (d, J=8.4 Hz, 1H), 7.61 (d, J=7.5 Hz, 2H), 7.49 (t, J=7.5 Hz, 2H), 7.39 (t, J=7.3 Hz, 1H), 6.71 (d, J=8.5 Hz, 2H), 6.38 (t, J=5.5 Hz, 1H), 4.58 (s, 2H), 3.23 (q, J=6.3 Hz, 4H), 2.63 (t, J=6.7 Hz, 2H), 1.70 (p, J=3.0 Hz, 4H); [M+H]+: 441.
    • Example 318 N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00343
  • 1H NMR (400 MHz, DMSO-d6) δ 11.40 (s, 1H), 8.86 (s, 1H), 8.50 (d, J=8.2 Hz, 1H), 7.74 (d, J=8.6 Hz, 2H), 7.47 (d, J=8.4 Hz, 1H), 7.40 (t, J=7.9 Hz, 1H), 7.31 (d, J=7.3 Hz, 1H), 7.14 (d, J=8.5 Hz, 1H), 7.04 (t, J=7.5 Hz, 1H), 6.71 (d, J=8.5 Hz, 2H), 6.37 (d, J=5.7 Hz, 1H), 4.25 (s, 2H), 3.77 (s, 3H), 3.23 (d, J=6.1 Hz, 4H), 2.63 (t, J=6.7 Hz, 2H), 1.70 (s, 4H); [M+H]+: 471.
    • Example 319 4-(4-Methylpiperazin-1-yl)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00344
  • 1H NMR (400 MHz, DMSO-d6) δ 11.62 (s, 1H), 10.13 (s, 1H), 9.07 (s, 1H), 8.57 (d, J=8.5 Hz, 1H), 7.89 (d, J=8.8 Hz, 2H), 7.70 (d, J=8.5 Hz, 1H), 7.66-7.58 (m, 2H), 7.49 (t, J=7.6 Hz, 2H), 7.40 (t, J=7.4 Hz, 1H), 7.19 (d, J=8.7 Hz, 2H), 4.60 (s, 2H), 4.09 (br s, 2H), 3.52 (br s, 2H), 3.17 (br s, 4H), 2.84 (s, 3H); [M+H]+: 427.
    • Example 320 4-Morpholino-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00345
  • 1H NMR (400 MHz, DMSO-d6) δ 11.59 (s, 1H), 9.03 (s, 1H), 8.57 (d, J=8.5 Hz, 1H), 7.86 (d, J=8.6 Hz, 2H), 7.69 (d, J=8.5 Hz, 1H), 7.65-7.58 (m, 2H), 7.49 (t, J=7.5 Hz, 2H), 7.40 (t, J=7.4 Hz, 1H), 7.10 (d, J=8.6 Hz, 2H), 4.59 (s, 2H), 3.76 (t, J=4.9 Hz, 4H); [M+H]+: 414.
    • Example 321 4-((2-Methoxyethyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00346
  • 1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 9.00 (s, 1H), 8.57 (d, J=8.4 Hz, 1H), 7.74 (d, J=8.5 Hz, 2H), 7.67 (d, J=8.5 Hz, 1H), 7.61 (d, J=7.6 Hz, 2H), 7.48 (t, J=7.6 Hz, 2H), 7.39 (t, J=7.3 Hz, 1H), 6.73 (d, J=8.5 Hz, 2H), 6.50 (t, J=5.6 Hz, 1H), 4.58 (s, 2H), 3.52 (t, J=5.5 Hz, 2H); [M+H]+: 402.
    • Example 322 4-((2-Morpholinoethyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00347
  • 1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 9.01 (s, 1H), 8.57 (d, J=8.4 Hz, 1H), 7.74 (d, J=8.3 Hz, 2H), 7.64 (dd, J=23.3, 8.0 Hz, 3H), 7.48 (t, J=7.5 Hz, 2H), 7.40 (d, J=7.5 Hz, 1H), 6.72 (d, J=8.5 Hz, 2H), 6.35 (s, 1H), 4.58 (s, 2H), 3.63-3.56 (m, 4H), 3.24 (s, 2H), 2.44 (s, 6H); [M+H]+: 457.
    • Example 323 N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-morpholino benzamide
  • Figure US20160311772A1-20161027-C00348
  • 1H NMR (400 MHz, DMSO-d6) δ 11.51 (s, 1H), 8.89 (s, 1H), 8.51 (d, J=8.4 Hz, 1H), 7.86 (d, J=8.6 Hz, 2H), 7.49 (d, J=8.4 Hz, 1H), 7.40 (s, 1H), 7.31 (dd, J=7.5, 1.8 Hz, 1H), 7.14 (d, J=8.3 Hz, 1H), 7.10 (d, J=8.7 Hz, 2H), 7.04 (t, J=7.4 Hz, 1H), 4.26 (s, 2H), 3.76 (d, J=4.0 Hz, 8H), 2.08 (s, 3H); [M+H]+: 444.
    • Example 324 4-((2-Methoxyethyl)amino)-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00349
  • 1H NMR (400 MHz, DMSO-d6) δ 11.40 (s, 1H), 8.86 (s, 1H), 8.50 (d, J=8.4 Hz, 1H), 7.77-7.69 (m, 2H), 7.46 (dd, J=8.5, 1.5 Hz, 1H), 7.39 (t, J=7.9 Hz, 1H), 7.34-7.27 (m, 1H), 7.13 (d, J=8.2 Hz, 1H), 7.04 (t, J=7.5 Hz, 1H), 6.76-6.69 (m, 2H), 6.49 (s, 1H), 4.25 (s, 2H), 3.76 (d, J=1.6 Hz, 3H), 3.51 (t, J=5.6 Hz, 2H); [M+H]+: 432.
    • Example 325 N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-(4-methyl piperazin-1-yl)benzamide
  • Figure US20160311772A1-20161027-C00350
  • 1H NMR (400 MHz, DMSO-d6) δ 11.49 (s, 1H), 8.89 (s, 1H), 8.50 (d, J=8.3 Hz, 1H), 7.83 (d, J=8.5 Hz, 2H), 7.48 (d, J=8.4 Hz, 1H), 7.40 (t, J=7.8 Hz, 1H), 7.35-7.28 (m, 1H), 7.14 (d, J=8.4 Hz, 1H), 7.11-7.02 (m, 3H), 4.25 (s, 2H), 3.77 (s, 3H), 3.33 (t, J=5.1 Hz, 4H), 2.46 (d, J=4.8 Hz, 4H), 2.23 (s, 3H); [M+H]+: 457.
    • Example 326 N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-(2-morpholinoethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00351
  • 1H NMR (400 MHz, DMSO-d6) δ 11.40 (s, 1H), 8.85 (s, 1H), 8.50 (d, J=8.4 Hz, 1H), 7.74 (d, J=8.5 Hz, 2H), 7.47 (d, J=8.3 Hz, 1H), 7.43-7.37 (m, 1H), 7.30 (dd, J=7.4, 1.8 Hz, 1H), 7.14 (d, J=8.3 Hz, 1H), 7.04 (t, J=7.4 Hz, 1H), 6.72 (d, J=8.7 Hz, 2H), 6.32 (t, J=5.5 Hz, 1H), 4.25 (s, 2H), 3.77 (s, 3H), 3.60 (t, J=4.6 Hz, 4H), 3.24 (q, J=6.3 Hz, 2H), 2.53 (d, J=6.7 Hz, 2H), 2.44 (t, J=4.7 Hz, 4H); [M+H]+: 487.
    • Example 327 4-((3-Morpholinopropyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00352
  • 1H NMR (400 MHz, DMSO-d6) δ 11.47 (s, 1H), 9.00 (s, 1H), 8.57 (d, J=8.5 Hz, 1H), 7.74 (d, J=8.5 Hz, 2H), 7.67 (d, J=8.5 Hz, 1H), 7.61 (d, J=7.5 Hz, 2H), 7.48 (t, J=7.6 Hz, 2H), 7.39 (t, J=7.4 Hz, 1H), 6.69 (d, J=8.4 Hz, 2H), 6.51 (t, J=5.6 Hz, 1H), 4.58 (s, 2H), 3.59 (t, J=4.6 Hz, 4H), 3.15 (q, J=6.5 Hz, 2H), 2.43-2.33 (m, 4H), 1.72 (p, J=6.9 Hz, 2H); [M+H]+: 471.
    • Example 328 N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-(3-morpholinopropyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00353
  • 1H NMR (400 MHz, DMSO-d6) δ 11.39 (s, 1H), 8.85 (s, 1H), 8.50 (d, J=8.3 Hz, 1H), 7.74 (d, J=8.4 Hz, 2H), 7.46 (d, J=8.4 Hz, 1H), 7.43-7.36 (m, 1H), 7.30 (dd, J=7.5, 1.7 Hz, 1H), 7.14 (d, J=8.3 Hz, 1H), 7.04 (t, J=7.4 Hz, 1H), 6.69 (d, J=8.5 Hz, 2H), 6.50 (t, J=5.5 Hz, 1H), 4.25 (s, 2H), 3.77 (s, 3H), 3.59 (t, J=4.6 Hz, 4H), 3.15 (q, J=6.5 Hz, 2H), 2.46-2.33 (m, 6H), 1.71 (q, J=7.0 Hz, 2H); [M+H]+: 501.
    • Example 329 4-((3-(4-Methylpiperazin-1-yl)propyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00354
  • 1H NMR (400 MHz, DMSO-d6) δ 11.47 (s, 1H), 9.00 (s, 1H), 8.57 (d, J=8.5 Hz, 1H), 7.74 (d, J=8.4 Hz, 2H), 7.67 (d, J=8.4 Hz, 1H), 7.61 (d, J=7.6 Hz, 2H), 7.49 (t, J=7.6 Hz, 2H), 7.39 (t, J=7.4 Hz, 1H), 6.68 (d, J=8.5 Hz, 2H), 6.52 (t, J=5.4 Hz, 1H), 4.58 (s, 2H), 3.14 (t, J=6.3 Hz, 2H), 2.42-2.25 (m, 10H), 2.15 (s, 3H), 1.75-1.66 (m, 2H); [M+H]+: 484.
    • Example 330 N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-(4-methyl piperazin-1-yl)propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00355
  • 1H NMR (400 MHz, DMSO-d6) δ 11.39 (s, 1H), 8.85 (s, 1H), 8.50 (d, J=8.5 Hz, 1H), 7.73 (d, J=8.4 Hz, 2H), 7.46 (d, J=8.4 Hz, 1H), 7.40 (t, J=7.9 Hz, 1H), 7.30 (d, J=7.4 Hz, 1H), 7.14 (d, J=8.3 Hz, 1H), 7.04 (t, J=7.4 Hz, 1H), 6.68 (d, J=8.4 Hz, 2H), 6.50 (d, J=6.2 Hz, 1H), 4.25 (s, 2H), 3.77 (s, 3H), 3.17-3.08 (m, 2H), 2.43-2.25 (m, 10H), 2.15 (s, 3H), 1.75-1.66 (m, 2H); [M+H]+: 514.
    • Example 331 4-((3-Methoxypropyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00356
  • 1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 9.00 (s, 1H), 8.57 (d, J=8.5 Hz, 1H), 7.74 (d, J=8.4 Hz, 2H), 7.67 (d, J=8.5 Hz, 1H), 7.61 (d, J=7.5 Hz, 2H), 7.48 (t, J=7.5 Hz, 2H), 7.39 (t, J=7.3 Hz, 1H), 6.68 (d, J=8.5 Hz, 2H), 6.48 (t, J=5.5 Hz, 1H), 4.58 (s, 2H), 3.43 (t, J=6.2 Hz, 2H), 3.26 (s, 3H), 3.16 (q, J=6.5 Hz, 2H), 1.80 (p, J=6.6 Hz, 2H); [M+H]+: 416.
    • Example 332 N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-methoxy propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00357
  • 1H NMR (400 MHz, DMSO-d6) δ 11.39 (s, 1H), 8.86 (s, 1H), 8.50 (d, J=8.3 Hz, 1H), 7.74 (d, J=8.4 Hz, 2H), 7.46 (d, J=8.4 Hz, 1H), 7.43-7.36 (m, 1H), 7.30 (dd, J=7.4, 1.7 Hz, 1H), 7.14 (d, J=8.2 Hz, 1H), 7.04 (t, J=7.4 Hz, 1H), 6.68 (d, J=8.4 Hz, 2H), 6.47 (t, J=5.6 Hz, 1H), 4.25 (s, 2H), 3.77 (s, 3H), 3.43 (t, J=6.2 Hz, 2H), 3.26 (s, 3H), 3.16 (q, J=6.5 Hz, 2H), 1.80 (p, J=6.6 Hz, 2H); [M+H]+: 446.
    • Example 333 N-(3-oxo-7-phenylisoindolin-4-yl)-4-((thiophen-2-ylmethyl) amino)benzamide
  • Figure US20160311772A1-20161027-C00358
  • 1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 9.00 (s, 1H), 8.56 (d, J=8.5 Hz, 1H), 7.73 (d, J=8.6 Hz, 2H), 7.67 (d, J=8.5 Hz, 1H), 7.61 (d, J=7.8 Hz, 2H), 7.48 (t, J=7.4 Hz, 2H), 7.43-7.35 (m, 2H), 7.10 (t, J=5.4 Hz, 2H), 6.99 (dd, J=5.1, 3.5 Hz, 1H), 6.78 (d, J=8.5 Hz, 2H), 4.63-4.53 (m, 4H); [M+H]+: 440.
    • Example 334 N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((thiophen-2-ylmethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00359
  • 1H NMR (400 MHz, DMSO-d6) δ 11.40 (s, 1H), 8.86 (s, 1H), 8.49 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.4 Hz, 2H), 7.46 (d, J=8.3 Hz, 1H), 7.39 (d, J=4.8 Hz, 2H), 7.30 (d, J=7.4 Hz, 1H), 7.17-7.07 (m, 3H), 7.04 (t, J=7.3 Hz, 1H), 6.99 (t, J=4.3 Hz, 1H), 6.78 (d, J=8.4 Hz, 2H), 4.56 (d, J=6.0 Hz, 2H), 4.24 (s, 2H), 3.76 (s, 3H); [M+H]+: 470.
    • Example 335 4-((3-(Dimethylamino)propyl)amino)-N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00360
  • 1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 9.13 (s, 1H), 8.54 (d, J=8.6 Hz, 1H), 7.93 (d, J=8.6 Hz, 1H), 7.82 (d, J=1.7 Hz, 1H), 7.72 (d, J=8.8 Hz, 2H), 6.84 (d, J=3.0 Hz, 1H), 6.68-6.65 (m, 3H), 6.55 (t, J=5.2 Hz, 1H), 4.63 (s, 2H), 3.12 (q, J=6.5 Hz, 2H), 2.29 (t, J=7.0 Hz, 2H), 2.14 (s, 6H), 1.69 (quint, J=6.9 Hz, 2H); [M+H]+: 404.
    • Example 336 N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((3-methoxypropyl) amino)benzamide
  • Figure US20160311772A1-20161027-C00361
  • 1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 9.12 (s, 1H), 8.54 (d, J=8.6 Hz, 1H), 7.93 (d, J=8.6 Hz, 1H), 7.82 (d, J=1.2 Hz, 1H), 7.72 (d, J=8.8 Hz, 2H), 6.84 (d, J=3.3 Hz, 1H), 6.68-6.65 (m, 3H), 6.53 (t, J=5.4 Hz, 1H), 4.63 (s, 2H), 3.42 (t, J=6.2 Hz, 2H), 3.25 (s, 3H), 3.15 (q, J=6.8 Hz, 2H), 1.79 (quint, J=6.6 Hz, 2H); [M+H]+: 391.
    • Example 337 N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((3-morpholino propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00362
  • 1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 9.13 (s, 1H), 8.54 (d, J=8.6 Hz, 1H), 7.93 (d, J=8.6 Hz, 1H), 7.82 (d, J=1.5 Hz, 1H), 7.72 (d, J=8.8 Hz, 2H), 6.84 (d, J=3.4 Hz, 1H), 6.69-6.65 (m, 3H), 6.56 (t, J=5.5 Hz, 1H), 4.63 (s, 2H), 3.58 (t, J=4.4 Hz, 5H), 3.14 (q, J=6.6 Hz, 2H), 2.36 (d, J=6.6 Hz, 5H), 1.71 (quint, J=6.8 Hz, 2H); [M+H]+: 446.
    • Example 338 N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl) propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00363
  • 1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 9.13 (s, 1H), 8.54 (d, J=8.7 Hz, 1H), 7.93 (d, J=8.6 Hz, 1H), 7.82 (d, J=1.3 Hz, 1H), 7.72 (d, J=8.8 Hz, 2H), 6.84 (d, J=3.3 Hz, 1H), 6.68-6.65 (m, 3H), 6.59 (t, J=5.5 Hz, 1H), 4.63 (s, 2H), 3.12 (q, J=6.5 Hz, 2H), 2.34-2.31 (m, 5H), 1.70 (quint, J=6.8 Hz, 2H), 1.50 (quint, J=5.4 Hz, 5H), 1.39-1.38 (m, 2H); [M+H]+: 444.
    • Example 339 N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl) propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00364
  • 1H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 9.13 (s, 1H), 8.54 (d, J=8.6 Hz, 1H), 7.93 (d, J=8.7 Hz, 1H), 7.82 (s, 1H), 7.72 (d, J=8.5 Hz, 2H), 6.84 (d, J=3.2 Hz, 1H), 6.68-6.66 (m, 3H), 6.56 (t, J=5.4 Hz, 1H), 4.63 (s, 2H), 3.15 (q, J=6.2 Hz, 2H), 2.47-2.42 (m, 5H), 1.74-1.68 (m, 7H); [M+H]+: 430.
    • Example 340 4-(4-Aminopiperidin-1-yl)-N-(3-oxo-7-phenylisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00365
  • 1H NMR (400 MHz, DMSO-d6) δ 11.55 (s, 1H), 9.05 (s, 1H), 8.57 (d, J=8.4 Hz, 1H), 7.81 (d, J=8.8 Hz, 2H), 7.68 (d, J=8.4 Hz, 1H), 7.61 (d, J=7.2 Hz, 2H), 7.48 (t, J=7.6 Hz, 2H), 7.39 (t, J=7.2 Hz, 1H), 7.50 (d, J=8.8 Hz, 2H), 4.59 (s, 2H), 3.86 (d, J=12.8 Hz, 2H), 2.94-2.88 (m, 2H), 2.81-2.75 (m, 1H), 1.79-1.75 (m, 2H), 1.31-1.23 (m, 2H). [M+H]+: 427.
    • Example 341 N-(7-(benzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)-4-((2-(dimethylamino)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00366
  • 1H NMR (400 MHz, DMSO-d6) δ 11.53 (s, 1H), 9.08 (s, 1H), 8.81 (s, 1H), 8.63 (d, J=8.4 Hz, 1H), 7.85 (t, J=7.8 Hz, 2H), 7.76 (d, J=8.8 Hz, 2H), 7.65 (d, J=7.2 Hz, 1H), 7.51 (t, J=7.8 Hz, 1H), 6.74 (d, J=8.8 Hz, 2H), 6.41 (t, J=5.2 Hz, 1H), 4.53 (s, 2H), 3.24 (d, J=6.0 Hz, 2H), 2.62-2.56 (m, 2H), 2.29 (s, 6H). [M+H]+: 456.
    • Example 342 N-(7-(benzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00367
  • 1H NMR (400 MHz, DMSO-d6) δ 11.52 (s, 1H), 9.07 (s, 1H), 8.81 (s, 1H), 8.63 (d, J=8.4 Hz, 1H), 7.85 (t, J=7.6 Hz, 2H), 7.76 (d, J=8.8 Hz, 2H), 7.65 (d, J=7.2 Hz, 1H), 7.51 (t, J=7.8 Hz, 1H), 6.72 (d, J=8.8 Hz, 2H), 6.36 (t, J=5.2 Hz, 1H), 4.53 (s, 2H), 3.22 (d, J=6.0 Hz, 2H), 2.44-2.36 (m, 4H), 1.53-1.50 (m, 4H), 1.40-1.38 (m, 2H). [M+H]+: 496.
    • Example 343 N-(7-(benzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00368
  • 1H NMR (400 MHz, DMSO-d6) δ 11.52 (s, 1H), 9.07 (s, 1H), 8.81 (s, 1H), 8.62 (d, J=8.4 Hz, 1H), 7.85 (t, J=7.8 Hz, 2H), 7.75 (d, J=8.8 Hz, 2H), 7.65 (d, J=7.2 Hz, 1H), 7.51 (t, J=7.8 Hz, 1H), 6.74 (d, J=8.8 Hz, 2H), 6.60 (t, J=5.2 Hz, 1H), 4.53 (s, 2H), 3.14 (d, J=6.0 Hz, 2H), 2.46-2.30 (m, 6H), 1.73-1.69 (m, 2H), 1.53-1.49 (m, 4H), 1.40-1.36 (m, 2H). [M+H]+: 510.
    • Example 344 4-((2-(Azepan-1-yl)ethyl)amino)-N-(7-(benzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00369
  • 1H NMR (400 MHz, DMSO-d6) δ 11.52 (s, 1H), 9.07 (s, 1H), 8.81 (s, 1H), 8.63 (d, J=8.4 Hz, 1H), 7.85 (t, J=7.6 Hz, 2H), 7.75 (d, J=8.8 Hz, 2H), 7.65 (d, J=7.2 Hz, 1H), 7.51 (t, J=7.8 Hz, 1H), 6.72 (d, J=8.8 Hz, 2H), 6.32 (t, J=5.0 Hz, 1H), 4.53 (s, 2H), 3.20 (d, J=6.0 Hz, 2H), 2.69-2.65 (m, 6H), 1.60-1.54 (m, 8H). [M+H]+: 510.
    • Example 345 4-(2-Morpholinoethoxy)-N-(3-oxo-7-phenylisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00370
  • 1H NMR (400 MHz, DMSO-d6) δ 11.66 (s, 1H), 9.10 (s, 1H), 8.56 (d, J=8.4 Hz, 1H), 7.93 (d, J=8.8 Hz, 2H), 7.93 (d, J=8.8 Hz, 2H), 7.70 (d, J=8.4 Hz, 1H), 7.62 (d, J=7.2 Hz, 2H), 7.49 (t, J=7.4 Hz, 2H), 7.40 (t, J=7.4 Hz, 1H), 7.16 (d, J=8.8 Hz, 2H), 4.61 (s, 2H), 4.20 (t, J=5.6 Hz, 2H), 3.58 (t, J=4.6 Hz, 4H), 2.78 (t, J=5.8 Hz, 2H), 2.53-2.50 (m, 4H). [M+H]+: 458.
    • Example 346 N-(3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino) benzamide
  • Figure US20160311772A1-20161027-C00371
  • 1H NMR (400 MHz, DMSO-d6) δ 11.26 (s, 1H), 8.88 (s, 1H), 8.43 (d, J=8.0 Hz, 1H), 7.79 (d, J=9.2 Hz, 2H), 7.72 (t, J=9.2 Hz, 1H), 7.20 (d, J=7.2 Hz, 1H), 6.69 (d, J=8.8 Hz, 2H), 6.40 (t, J=6.0 Hz, 1H), 4.41 (s, 2H), 3.21 (q, J=6.0 Hz, 2H), 2.62 (t, J=6.6 Hz, 2H), 1.71-1.66 (m, 4H). [M+H]+: 365.
    • Example 347 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-(2-morpholinoethoxy)benzamide
  • Figure US20160311772A1-20161027-C00372
  • 1H NMR (400 MHz, DMSO-d6) δ 11.57 (s, 1H), 8.97 (s, 1H), 8.51 (d, J=8.4 Hz, 1H), 7.93 (d, J=8.8 Hz, 2H), 7.53 (d, J=8.4 Hz, 1H), 7.17-7.10 (m, 4H), 6.95 (dd, J=7.2, 1.6 Hz, 1H), 4.30 (s, 2H), 4.20 (t, J=5.8 Hz, 2H), 3.85 (s, 3H), 3.58 (t, J=4.8 Hz, 4H), 3.45 (s, 3H), 2.73 (t, J=5.6 Hz, 2H), 2.53-2.50 (m, 4H). [M+H]+: 518.
    • Example 348 N-(7-(3-amino-2-hydroxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-morpholinoethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00373
  • 1H NMR (400 MHz, DMSO-d6) δ 11.41 (s, 1H), 8.87 (s, 1H), 8.49 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.45 (d, J=8.4 Hz, 1H), 6.71 (d, J=8.8 Hz, 2H), 6.68-6.66 (m, 2H), 6.44 (dd, J=6.2, 3.0 Hz, 1H), 6.37 (d, J=5.4 Hz, 1H), 4.28 (s, 2H), 3.59 (t, J=4.4 Hz, 4H), 3.23 (q, J=6.0 Hz, 2H), 2.53-2.50 (m, 2H), 2.46-2.40 (m. 4H). [M+H]+: 488.
    • Example 349 4-((2-(Azepan-1-yl)ethyl)amino)-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00374
  • 1H NMR (400 MHz, DMSO-d6) δ 11.40 (s, 1H), 8.90 (s, 1H), 8.49 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.4 Hz, 2H), 7.46 (d, J=8.4 Hz, 1H), 7.39 (d, J=7.6 Hz, 1H), 7.30 (dd, J=7.4, 1.4 Hz, 1H), 7.13 (d, J=8.4 Hz, 1H), 7.04 (t, J=7.6 Hz, 1H), 6.71 (d, J=7.6 Hz, 2H), 6.29 (t, J=5.4 Hz, 1H), 4.25 (s, 2H), 3.76 (s, 3H), 3.18-3.15 (m, 2H), 2.68-2.64 (m, 6H), 1.58-1.55 (m, 8H). [M+H]+: 499.
    • Example 350 4-((2-(Azepan-1-yl)ethyl)amino)-N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00375
  • 1H NMR (400 MHz, DMSO-d6) δ 11.40 (s, 1H), 8.92 (s, 1H), 8.51 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.50 (d, J=8.4 Hz, 1H), 7.16-7.09 (m, 2H), 6.94 (dd, J=7.2, 1.6 Hz, 1H), 6.71 (d, J=8.8 Hz, 2H), 6.29 (t, J=5.4 Hz, 1H), 4.29 (s, 2H), 3.85 (s, 3H), 3.44 (s, 3H), 3.20-3.16 (m, 2H), 2.68-2.64 (m, 6H), 1.58-1.55 (m, 8H). [M+H]+: 529.
    • Example 351 4-((3-(Dimethylamino)propyl)amino)-N-(7-(2-hydroxyphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00376
  • 1H NMR (400 MHz, DMSO-d6) δ 11.40 (s, 1H), 8.85 (s, 1H), 8.49 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.4 Hz, 2H), 7.48 (d, J=8.4 Hz, 1H), 7.23-7.17 (m, 2H), 6.94 (d, J=8.0 Hz, 1H), 6.84 (t, J=7.6 Hz, 1H), 6.67 (d, J=8.8 Hz, 2H), 6.49 (t, J=5.4 Hz, 1H), 4.34 (s, 2H), 3.12 (q, J=6.4 Hz, 2H), 2.30 (t, J=7.0 Hz, 2H), 2.14 (s, 6H), 1.69 (quint, J=7.0 Hz, 2H). [M+H]+: 445.
    • Example 352 4-((2-Hydroxyethyl)amino)-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00377
  • 1H NMR (400 MHz, DMSO-d6) δ 11.40 (s, 1H), 8.88 (s, 1H), 8.50 (d, J=8.0 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.46 (d, J=8.4 Hz, 1H), 7.40 (td, J=7.8, 1.6 Hz, 1H), 7.31 (dd, J=7.4, 1.8 Hz, 1H), 7.13 (d, J=8.0 Hz, 1H), 7.03 (td, J=7.4, 0.8 Hz, 1H), 6.71 (d, J=8.8 Hz, 2H), 6.46 (t, J=5.6 Hz, 1H), 4.76 (t, J=5.0 Hz, 1H), 4.25 (s, 2H), 3.76 (s, 3H), 3.58 (q, J=5.2 Hz, 2H), 3.16 (q, J=5.6 Hz, 2H). [M+H]+: 418.
    • Example 353 4-((2-Hydroxyethyl)amino)-N-(7-(2-hydroxyphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00378
  • 1H NMR (400 MHz, DMSO-d6) δ 11.40 (s, 1H), 9.65 (br.s, 1H), 8.85 (s, 1H), 8.50 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.4 Hz, 2H), 7.49 (d, J=8.4 Hz, 1H), 7.21 (td, J=5.6, 1.6 Hz, 2H), 6.96 (d, J=8.0 Hz, 1H), 6.88 (t, J=7.4 Hz, 1H), 6.71 (d, J=8.8 Hz, 2H), 6.45 (t, J=5.6 Hz, 1H), 4.75 (t, J=5.4 Hz, 1H), 4.33 (s, 2H), 3.58 (q, J=5.6 Hz, 2H), 3.18 (q, J=5.6 Hz, 2H). [M+H]+: 404.
    • Example 354 4-(3-Hydroxypropyl)amino)-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00379
  • 1H NMR (400 MHz, DMSO-d6) δ 11.40 (s, 1H), 8.88 (s, 1H), 8.50 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.46 (d, J=8.4 Hz, 1H), 7.40 (td, J=7.8, 1.6 Hz, 1H), 7.31 (dd, J=7.2, 1.6 Hz, 1H), 7.13 (d, J=8.0 Hz, 1H), 7.04 (t, J=7.6 Hz, 1H), 6.68 (d, J=8.8 Hz, 2H), 6.47 (t, J=5.4 Hz, 1H), 4.52 (t, J=5.0 Hz, 1H), 4.25 (s, 2H), 3.76 (s, 3H), 3.51 (q, J=5.2 Hz, 2H), 3.16 (q, J=6.4 Hz, 2H), 1.72 (quint, J=6.6 Hz, 2H). [M+H]+: 432.
    • Example 355 N-(7-(2-hydroxyphenyl)-3-oxoisoindolin-4-yl)-4-(3-hydroxypropyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00380
  • 1H NMR (400 MHz, DMSO-d6) δ 11.40 (s, 1H), 9.77 (br.s, 1H), 8.85 (s, 1H), 8.49 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.48 (d, J=8.4 Hz, 1H), 7.24-7.18 (m, 2H), 6.96 (d, J=8.0 Hz, 1H), 6.87 (t, J=7.6 Hz, 1H), 7.13 (d, J=8.4 Hz, 2H), 6.46 (t, J=5.2 Hz, 1H), 4.52 (t, J=5.0 Hz, 1H), 4.33 (s, 2H), 3.52 (q, J=5.2 Hz, 2H), 3.16 (q, J=6.4 Hz, 2H), 1.72 (quint, J=6.4 Hz, 2H). [M+H]+: 418.
    • Example 356 4-((4-Hydroxybutyl)amino)-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00381
  • 1H NMR (400 MHz, DMSO-d6) δ 11.39 (s, 1H), 8.88 (s, 1H), 8.50 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.46 (d, J=8.4 Hz, 1H), 7.40 (td, J=7.8, 1.6 Hz, 1H), 7.30 (dd, J=7.6, 1.6 Hz, 1H), 7.13 (d, J=8.0 Hz, 1H), 7.04 (t, J=7.4 Hz, 1H), 6.68 (d, J=8.4 Hz, 2H), 6.49 (t, J=5.4 Hz, 1H), 4.43 (t, J=4.8 Hz, 1H), 4.25 (s, 2H), 3.76 (s, 3H), 3.44 (q, J=5.2 Hz, 2H), 3.10 (q, J=6.4 Hz, 2H), 1.62-1.50 (m, 4H). [M+H]+: 446.
    • Example 357 4-((4-Hydroxybutyl)amino)-N-(7-(2-hydroxyphenyl)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00382
  • 1H NMR (400 MHz, DMSO-d6) δ 11.40 (s, 1H), 9.73 (br.s, 1H), 8.85 (s, 1H), 8.49 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.4 Hz, 2H), 7.48 (d, J=8.4 Hz, 1H), 7.24-7.19 (m, 2H), 6.96 (d, J=8.0 Hz, 1H), 6.88 (t, J=7.4 Hz, 1H), 6.68 (d, J=8.8 Hz, 2H), 6.48 (t, J=5.2 Hz, 1H), 4.43 (t, J=4.8 Hz, 1H), 4.33 (s, 2H), 3.44 (q, J=5.6 Hz, 2H), 3.10 (q, J=6.0 Hz, 2H), 1.62-1.50 (m, 4H). [M+H]+: 432.
    • Example 358 4-(Methyl(2-(methylamino)ethyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00383
  • 1H NMR (400 MHz, DMSO-d6) δ 11.53 (s, 1H), 9.04 (s, 1H), 8.57 (d, J=8.4 Hz, 1H), 7.80 (d, J=8.8 Hz, 2H), 7.67 (d, J=8.4 Hz, 1H), 7.62-7.60 (m, 2H), 7.48 (t, J=7.6 Hz, 2H), 7.39 (t, J=7.4 Hz, 1H), 6.83 (d, J=9.2 Hz, 2H), 4.59 (s, 2H), 3.49 (t, J=6.8 Hz, 2H), 3.02 (s, 3H), 2.65 (t, J=6.6 Hz, 2H), 2.30 (s, 3H). [M+H]+: 415.
    • Example 359 N-(7-(2,3-difluorophenyl)-3-oxoisoindolin-4-yl)-4-((2-morpholinoethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00384
  • 1H NMR (400 MHz, DMSO-d6) δ 11.46 (s, 1H), 9.02 (s, 1H), 8.57 (d, J=8.4 Hz, 1H), 7.74 (d, J=8.8 Hz, 2H), 7.62 (d, J=8.4 Hz, 1H), 7.59 (q, J=8.8 Hz, 1H), 7.40 (t, J=7.4 Hz, 1H), 7.34-7.31 (m, 1H), 6.72 (d, J=8.8 Hz, 2H), 6.38 (t, J=5.6 Hz, 1H), 4.40 (s, 2H), 3.59 (t, J=4.6 Hz, 4H), 3.23 (q, J=6.0 Hz, 2H), 2.55-2.52 (m, 2H), 2.46-2.42 (m, 4H). [M+H]+:493.
    • Example 360 N-(3-oxo-7-phenylisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl) amino)benzamide
  • Figure US20160311772A1-20161027-C00385
  • 1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 9.02 (s, 1H), 8.57 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.67 (d, J=8.4 Hz, 1H), 7.61 (d, J=7.2 Hz, 2H), 7.48 (t, J=7.6 Hz, 2H), 7.39 (t, J=7.2 Hz, 1H), 6.71 (d, J=8.8 Hz, 2H), 6.32 (t, J=5.4 Hz, 1H), 4.59 (s, 2H), 3.21 (q, J=6.0 Hz, 2H), 2.47-2.46 (m, 2H), 2.40-2.37 (m, 4H), 1.54-1.48 (m, 4H), 1.40-1.38 (m, 2H). [M+H]+: 455.
    • Example 361 N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00386
  • 1H NMR (400 MHz, DMSO-d6) δ 11.40 (s, 1H), 8.88 (s, 1H), 8.49 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.46 (d, J=8.4 Hz, 1H), 7.41-7.37 (m, 1H), 7.30 (dd, J=7.6, 1.6 Hz, 1H), 7.13 (d, J=8.0 Hz, 1H), 7.04 (t, J=7.4 Hz, 1H), 6.71 (d, J=8.8 Hz, 2H), 6.31 (t, J=5.2 Hz, 1H), 4.25 (s, 2H), 3.76 (s, 3H), 3.21 (q, J=6.0 Hz, 2H), 2.49-2.46 (m, 2H), 2.40-2.37 (m, 4H), 1.54-1.49 (m, 4H), 1.40-1.38 (m, 2H). [M+H]+: 485.
    • Example 362 4-((2-(Dimethylamino)ethyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00387
  • 1H NMR (400 MHz, DMSO-d6) δ 11.49 (s, 1H), 9.03 (s, 1H), 8.57 (d, J=8.4 Hz, 1H), 7.74 (d, J=8.8 Hz, 2H), 7.67 (d, J=8.4 Hz, 1H), 7.61 (d, J=7.2 Hz, 2H), 7.48 (t, J=7.6 Hz, 2H), 7.39 (t, J=7.4 Hz, 1H), 6.72 (d, J=8.8 Hz, 2H), 6.33 (t, J=5.2 Hz, 1H), 4.59 (s, 2H), 3.21-3.16 (m, 2H), 2.46 (t, J=6.6 Hz, 2H), 2.20 (s, 6H). [M+H]+: 415.
    • Example 363 N-(3-oxo-7-phenylisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl) propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00388
  • 1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 9.02 (s, 1H), 8.56 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.67 (d, J=8.8 Hz, 1H), 7.61 (d, J=7.2 Hz, 2H), 7.48 (t, J=7.6 Hz, 2H), 7.39 (t, J=7.2 Hz, 1H), 6.67 (d, J=8.8 Hz, 2H), 6.53 (t, J=5.4 Hz, 1H), 4.58 (s, 2H), 3.14 (q, J=6.8 Hz, 2H), 2.49-2.47 (m, 2H), 2.45-2.42 (m, 4H), 1.71 (quint, J=5.6 Hz, 2H), 1.69-1.67 (m, 4H). [M+H]+: 455.
    • Example 364 N-(7-(2,3-difluorophenyl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00389
  • 1H NMR (400 MHz, DMSO-d6) δ 11.51 (s, 1H), 9.44 (br.s, 1H), 9.04 (s, 1H), 8.57 (d, J=8.4 Hz, 1H), 7.80 (d, J=8.4 Hz, 2H), 7.63 (d, J=8.4 Hz, 1H), 7.51 (q, J=8.8 Hz, 1H), 7.40 (t, J=7.2 Hz, 1H), 7.34-7.29 (m, 1H), 6.79 (d, J=8.8 Hz, 2H), 6.67 (t, J=5.4 Hz, 1H), 4.41 (s, 2H), 3.64-3.60 (m, 2H), 3.56-3.51 (m, 2H), 3.12-3.06 (m, 2H), 2.55-2.52 (m, 2H), 2.08-1.98 (m, 2H), 1.88-1.85 (m, 2H). [M+H]+: 477.
    • Example 365 N-(7-(2,3-difluorophenyl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide hydrochloride
  • Figure US20160311772A1-20161027-C00390
  • 1H NMR (400 MHz, DMSO-d6) δ 11.51 (s, 1H), 10.43 (br.s, 1H), 9.06 (s, 1H), 8.57 (d, J=8.8 Hz, 1H), 7.79 (d, J=8.4 Hz, 2H), 7.63 (d, J=8.4 Hz, 1H), 7.46-7.53 (m, 1H), 7.42-7.39 (m, 1H), 7.34-7.29 (m, 1H), 6.81-6.79 (m, 3H), 4.41 (s, 2H), 3.60-3.55 (m, 5H), 3.32 (q, J=6.0 Hz, 2H), 3.04 (d, J=6.0 Hz, 2H), 2.03-1.97 (m, 2H), 1.89-1.86 (m, 2H). [M+H]+: 477.
    • Example 366 N-(7-(2,3-difluorophenyl)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide hydrochloride
  • Figure US20160311772A1-20161027-C00391
  • 1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 9.41 (br.s, 1H), 9.03 (s, 1H), 8.56 (d, J=8.4 Hz, 1H), 7.77 (d, J=8.4 Hz, 2H), 7.63 (d, J=8.0 Hz, 1H), 7.53-7.47 (m, 1H), 7.40 (t, J=7.2 Hz, 1H), 7.35-7.29 (m, 1H), 6.72 (d, J=8.8 Hz, 2H), 6.60 (t, J=5.6 Hz, 1H), 4.41 (s, 2H), 3.57-3.54 (m, 2H), 3.23-3.20 (m, 4H), 3.08-3.01 (m, 2H), 2.49-2.45 (m, 2H), 2.10-2.01 (m, 2H), 1.98-1.90 (m, 2H), 1.87-1.85 (m, 2H). [M+H]+: 491.
    • Example 367 N-(7-(2,3-difluorophenyl)-3-oxoisoindolin-4-yl)-4-((2-(dimethylamino)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00392
  • 1H NMR (400 MHz, DMSO-d6) δ 11.46 (s, 1H), 9.03 (s, 1H), 8.57 (d, J=8.8 Hz, 1H), 7.74 (d, J=8.8 Hz, 2H), 7.62 (d, J=8.4 Hz, 1H), 7.53-7.46 (m, 1H), 7.40 (t, J=6.6 Hz, 1H), 7.35-7.31 (m, 1H), 6.72 (d, J=8.8 Hz, 2H), 6.36 (t, J=5.2 Hz, 1H), 4.40 (s, 2H), 3.19 (q, J=6.0 Hz, 2H), 2.45 (d, J=6.6 Hz, 2H), 2.19 (s, 6H). [M+H]+: 451.
    • Example 368 N-(7-(2,3-difluorophenyl)-3-oxoisoindolin-4-yl)-4-((3-(dimethylamino)propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00393
  • 1H NMR (400 MHz, DMSO-d6) δ 11.46 (s, 1H), 9.03 (s, 1H), 8.57 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.62 (d, J=7.6 Hz, 1H), 7.52-7.46 (m, 1H), 7.40 (t, J=6.8 Hz, 1H), 7.34-7.29 (m, 1H), 6.67 (d, J=9.2 Hz, 2H), 6.54 (t, J=5.4 Hz, 1H), 4.40 (s, 2H), 3.13 (q, J=5.6 Hz, 2H), 2.29 (t, J=7.0 Hz, 2H), 2.14 (s, 6H) 1.68 (quint, J=7.0 Hz, 2H). [M+H]+: 465.
    • Example 369 4-((2-(Azepan-1-yl)ethyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00394
  • 1H NMR (400 MHz, DMSO-d6) δ 11.49 (s, 1H), 9.04 (s, 1H), 8.57 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.67 (d, J=8.4 Hz, 1H), 7.61 (d, J=7.6 Hz, 2H), 7.48 (t, J=7.6 Hz, 2H), 7.39 (t, J=7.2 Hz, 1H), 6.71 (d, J=8.8 Hz, 2H), 6.29 (t, J=5.6 Hz, 1H), 4.59 (s, 2H), 3.18 (q, J=6.4 Hz, 2H), 2.69-2.56 (m, 7H), 1.58-1.55 (m, 8H). [M+H]+: 469.
    • Example 370 N-(3-oxo-7-phenylisoindolin-4-yl)-4-((3-(piperidin-1-yl) propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00395
  • 1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 9.03 (s, 1H), 8.57 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.66 (d, J=8.4 Hz, 1H), 7.61 (d, J=7.2 Hz, 2H), 7.48 (t, J=7.6 Hz, 2H), 7.39 (t, J=7.4 Hz, 1H), 6.67 (d, J=8.8 Hz, 2H), 6.57 (t, J=5.4 Hz, 1H), 4.58 (s, 2H), 3.12 (q, J=6.4 Hz, 2H), 2.33 (t, J=6.8 Hz, 2H), 1.70 (quint, J=7.0 Hz, 2H), 1.53-1.46 (m, 4H), 1.39-1.36 (m, 2H). [M+H]+: 469.
    • Example 371 4-((2-Hydroxyethyl)amino)-N-(3-oxo-7-(thiophen-2-yl) isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00396
  • 1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 9.15 (s, 1H), 8.53 (d, J=8.4 Hz, 1H), 7.86 (d, J=8.8 Hz, 1H), 7.72 (d, J=8.4 Hz, 2H), 7.64 (d, J=5.2 Hz, 1H), 7.46 (d, J=3.6 Hz, 1H), 7.20 (t, J=4.4 Hz, 1H), 6.71 (d, J=8.8 Hz, 2H), 6.49 (t, J=5.4 Hz, 1H), 4.76 (t, J=5.4 Hz, 1H), 4.65 (s, 2H), 3.57 (q, J=6.0 Hz, 2H), 3.19 (q, J=6.0 Hz, 2H). [M+H]+: 394.
    • Example 372 4-((2-Methoxyethyl)amino)-N-(3-oxo-7-(thiophen-2-yl) isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00397
  • 1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 9.15 (s, 1H), 8.53 (d, J=8.4 Hz, 1H), 7.86 (d, J=8.4 Hz, 1H), 7.72 (d, J=8.8 Hz, 2H), 7.64 (d, J=4.4 Hz, 1H), 7.46 (d, J=3.2 Hz, 1H), 7.20 (dd, J=5.2, 3.6 Hz, 1H), 6.72 (d, J=8.8 Hz, 2H), 6.55 (t, J=5.6 Hz, 1H), 4.65 (s, 2H), 3.51 (t, J=5.6 Hz, 2H), 3.29 (s, 3H), 3.28 (t, J=8.2 Hz, 2H). [M+H]+: 408.
    • Example 373 4-((2-(Dimethylamino)ethyl)amino)-N-(3-oxo-7-(thiophen-2-yl)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00398
  • 1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 9.15 (s, 1H), 8.53 (d, J=8.4 Hz, 1H), 7.86 (d, J=8.4 Hz, 1H), 7.72 (d, J=8.8 Hz, 2H), 7.64 (dd, J=4.8, 0.8 Hz, 1H), 7.46 (d, J=2.8 Hz, 1H), 7.20 (dd, J=5.2, 3.6 Hz, 1H), 6.72 (d, J=9.2 Hz, 2H), 6.34 (t, J=5.4 Hz, 1H), 4.65 (s, 2H), 3.18 (q, J=6.0 Hz, 2H), 2.45 (t, J=6.6 Hz, 2H), 2.19 (s, 3H). [M+H]+: 421.
    • Example 374 N-(3-oxo-7-(thiophen-2-yl)isoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00399
  • 1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 9.15 (s, 1H), 8.53 (d, J=8.8 Hz, 1H), 7.86 (d, J=8.4 Hz, 1H), 7.72 (d, J=8.8 Hz, 2H), 7.64 (dd, J=4.8, 0.8 Hz, 1H), 7.46 (d, J=2.8 Hz, 1H), 7.20 (dd, J=5.2, 3.6 Hz, 1H), 6.70 (d, J=8.8 Hz, 2H), 6.34 (t, J=5.4 Hz, 1H), 4.65 (s, 2H), 3.20 (q, J=6.0 Hz, 2H), 2.47 (t, J=6.6 Hz, 2H), 2.42-2.37 (m, 4H), 1.53-1.48 (m, 4H), 1.39-1.36 (m, 2H). [M+H]+: 461.
    • Example 375 4-((2-Morpholinoethyl)amino)-N-(3-oxo-7-(thiophen-2-yl) isoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00400
  • 1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 9.15 (s, 1H), 8.53 (d, J=8.4 Hz, 1H), 7.86 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.64 (dd, J=5.2, 0.8 Hz, 1H), 7.46 (d, J=3.2 Hz, 1H), 7.20 (dd, J=5.2, 3.6 Hz, 1H), 6.71 (d, J=8.8 Hz, 2H), 6.38 (t, J=5.2 Hz, 1H), 4.65 (s, 2H), 3.59 (t, J=4.4 Hz, 4H), 3.23 (q, J=6.0 Hz, 2H), 2.53-2.50 (m, 2H), 2.46-2.40 (m, 4H). [M+H]+: 463.
    • Example 376 N-(7-(benzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00401
  • 1H NMR (400 MHz, DMSO-d6) δ 11.53 (s, 1H), 9.08 (s, 1H), 8.81 (s, 1H), 8.62 (d, J=8.4 Hz, 1H), 7.85 (t, J=7.6 Hz, 2H), 7.75 (d, J=8.8 Hz, 2H), 7.65 (d, J=7.2 Hz, 1H), 7.51 (t, J=7.8 Hz, 1H), 6.72 (d, J=8.8 Hz, 2H), 6.45 (t, J=5.2 Hz, 1H), 4.53 (s, 2H), 3.24 (d, J=6.0 Hz, 2H), 2.66-2.63 (m, 2H), 1.74-1.66 (m, 4H). [M+H]+: 482.
    • Example 377 N-(7-(2-methylbenzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00402
  • 1H NMR (400 MHz, DMSO-d6) δ 11.51 (s, 1H), 9.07 (s, 1H), 8.61 (d, J=8.4 Hz, 1H), 7.82 (d, J=8.8 Hz, 1H), 7.75 (d, J=8.8 Hz, 2H), 7.69 (d, J=8.0 Hz, 1H), 7.53 (d, J=6.8 Hz, 1H), 7.43 (t, J=7.8 Hz, 1H), 6.72 (d, J=8.8 Hz, 2H), 6.45 (t, J=5.2 Hz, 1H), 4.51 (s, 2H), 3.23 (d, J=6.4 Hz, 2H), 2.63 (t, J=6.8 Hz, 1H), 2.63 (s, 3H), 1.72-1.67 (m, 4H). [M+H]+: 496.
    • Example 378 4-((2-(4-Methylpiperazin-1-yl)ethyl)amino)-N-(3-oxo-7-(thiophen-2-yl)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00403
  • 1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 9.12 (s, 1H), 8.53 (d, J=8.8 Hz, 1H), 7.86 (d, J=8.8 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.64 (d, J=4.8 Hz, 1H), 7.46 (d, J=3.2 Hz, 1H), 7.20 (dd, J=5.0, 3.8 Hz, 1H), 6.70 (d, J=8.8 Hz, 2H), 6.35 (d, J=5.4 Hz, 1H), 4.65 (s, 2H), 3.21 (q, J=6.4 Hz, 2H), 2.46-2.30 (m, 8H), 2.15 (s, 3H). [M+H]+: 476.
    • Example 379 4-((2-(4-Methylpiperazin-1-yl)ethyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00404
  • 1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 9.02 (s, 1H), 8.56 (d, J=8.0 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.66 (d, J=8.4 Hz, 1H), 7.60 (d, J=7.6 Hz, 2H), 7.48 (t, J=7.6 Hz, 2H), 7.39 (t, J=7.4 Hz, 1H), 6.71 (d, J=8.8 Hz, 2H), 6.32 (t, J=5.4 Hz, 1H), 4.58 (s, 2H), 3.21 (q, J=6.4 Hz, 2H), 2.54-2.50 (m, 2H), 2.44 (br.s, 4H), 2.33 (br.s, 4H), 2.15 (s, 3H). [M+H]+: 470.
    • Example 380 4-((2-Hydroxyethyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00405
  • 1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 9.02 (s, 1H), 8.57 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.4 Hz, 2H), 7.67 (d, J=8.4 Hz, 1H), 7.61 (d, J=7.6 Hz, 2H), 7.48 (t, J=7.6 Hz, 2H), 7.39 (t, J=7.4 Hz, 1H), 6.71 (d, J=8.8 Hz, 2H), 6.47 (t, J=5.6 Hz, 1H), 4.76 (t, J=5.4 Hz, 1H), 4.59 (s, 2H), 3.58 (q, J=5.6 Hz, 2H), 3.19 (q, J=5.6 Hz, 2H). [M+H]+: 388.
    • Example 381 4-((3-(Dimethylamino)propyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00406
  • 1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 9.02 (s, 1H), 8.57 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.67 (d, J=8.4 Hz, 1H), 7.60 (d, J=7.2 Hz, 2H), 7.48 (t, J=7.6 Hz, 2H), 7.39 (t, J=7.4 Hz, 1H), 6.68 (d, J=8.8 Hz, 2H), 6.52 (t, J=5.4 Hz, 1H), 4.59 (s, 2H), 3.12 (q, J=6.8 Hz, 2H), 2.29 (t, J=7.2 Hz, 2H), 2.14 (s, 6H), 1.69 (qunt, J=6.8 Hz, 2H). [M+H]+: 429.
    • Example 382 4-((3-Hydroxypropyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00407
  • 1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 9.02 (s, 1H), 8.57 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.67 (d, J=8.8 Hz, 1H), 7.61 (d, J=7.2 Hz, 2H), 7.48 (t, J=7.6 Hz, 2H), 7.40 (t, J=7.4 Hz, 1H), 6.68 (d, J=8.8 Hz, 2H), 6.48 (t, J=5.2 Hz, 1H), 4.58 (s, 2H), 4.52 (t, J=5.0 Hz, 1H), 3.52 (q, J=5.2 Hz, 2H), 3.16 (q, J=6.4 Hz, 2H), 1.72 (qunt, J=6.6 Hz, 2H). [M+H]+:402.
    • Example 383 4-((4-Hydroxybutyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00408
  • 1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 9.02 (s, 1H), 8.57 (d, J=8.4 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.67 (d, J=8.4 Hz, 1H), 7.61 (d, J=7.2 Hz, 2H), 7.48 (t, J=7.6 Hz, 2H), 7.39 (t, J=7.4 Hz, 1H), 6.68 (d, J=8.4 Hz, 2H), 6.49 (t, J=5.4 Hz, 1H), 4.58 (s, 2H), 4.44 (t, J=5.0 Hz, 1H), 3.46-3.42 (m, 3H), 3.10 (q, J=6.4 Hz, 2H), 1.62-1.55 (m, 2H), 1.53-1.50 (m, 2H). [M+H]+:416.
    • Example 384 N-(7-(benzofuran-2-yl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00409
  • 1H NMR (400 MHz, DMSO-d6) δ 11.54 (s, 1H), 9.22 (s, 1H), 8.62 (d, J=8.7 Hz, 1H), 8.15 (d, J=8.6 Hz, 1H), 7.74 (d, J=8.7 Hz, 2H), 7.72-7.63 (m, 2H), 7.35 (td, J=8.2, 7.7, 1.5 Hz, 1H), 7.32-7.27 (m, 2H), 6.72 (d, J=8.8 Hz, 2H), 6.45 (t, J=5.5 Hz, 1H), 4.79 (s, 2H), 3.23 (q, J=6.4 Hz, 2H), 2.63 (t, J=6.7 Hz, 2H), 2.49 (s, 4H), 1.70 (p, J=3.0 Hz, 4H); [M+H]+: 481.
    • Example 385 N-(3-oxo-7-(quinolin-6-yl)isoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00410
  • 1H NMR (400 MHz, DMSO-d6) δ 9.12 (s, 1H), 8.94 (dd, J=4.2, 1.7 Hz, 1H), 8.63 (d, J=8.5 Hz, 1H), 8.46 (dd, J=8.5, 1.7 Hz, 1H), 8.25 (d, J=2.0 Hz, 1H), 8.12 (d, J=8.8 Hz, 1H), 8.08-7.99 (m, 2H), 7.85 (d, J=8.5 Hz, 1H), 7.82-7.75 (m, 2H), 7.60 (dd, J=8.3, 4.2 Hz, 1H), 6.77 (d, J=8.6 Hz, 2H), 6.60 (s, 1H), 4.72 (s, 2H), 3.27 (t, J=6.4 Hz, 2H), 2.90 (d, J=33.8 Hz, 4H), 2.72 (s, 2H), 1.81 (d, J=5.8 Hz, 4H); [M+H]+: 492.
    • Example 386 N-(3-oxo-7-(quinolin-5-yl)isoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00411
  • 1H NMR (400 MHz, CDCl3) δ 11.28 (s, 1H), 8.98 (dd, J=4.2, 1.6 Hz, 1H), 8.86 (d, J=8.4 Hz, 1H), 8.20 (d, J=8.5 Hz, 1H), 7.98 (t, J=8.9 Hz, 3H), 7.81 (dd, J=8.5, 7.1 Hz, 1H), 7.57 (d, J=8.4 Hz, 1H), 7.54 (dd, J=7.1, 1.2 Hz, 1H), 7.39 (dd, J=8.6, 4.2 Hz, 1H), 6.70 (d, J=8.5 Hz, 2H), 6.64 (s, 1H), 4.34-4.02 (m, 2H), 3.29 (q, J=5.6 Hz, 2H), 2.79 (t, J=6.0 Hz, 2H), 2.57 (d, J=5.9 Hz, 4H), 1.87-1.77 (m, 4H); [M+H]+: 492.
    • Example 387 N-(3-oxo-7-(quinolin-4-yl)isoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00412
  • 1H NMR (400 MHz, CDCl3) δ 11.30 (s, 1H), 9.00 (d, J=4.4 Hz, 1H), 8.88 (d, J=8.4 Hz, 1H), 8.22 (d, J=8.5 Hz, 1H), 8.00-7.94 (m, 2H), 7.78 (ddd, J=8.4, 6.8, 1.4 Hz, 1H), 7.69 (dd, J=8.6, 1.3 Hz, 1H), 7.61 (d, J=8.4 Hz, 1H), 7.54 (ddd, J=8.2, 6.8, 1.2 Hz, 1H), 7.38 (d, J=4.4 Hz, 1H), 6.74-6.65 (m, 3H), 4.23 (d, J=23.4 Hz, 2H), 3.29 (q, J=5.7 Hz, 2H), 2.79 (t, J=6.0 Hz, 2H), 2.59 (p, J=3.5 Hz, 4H), 1.88-1.76 (m, 4H); [M+H]+: 492.
    • Example 388 7-(4-Fluorobenzamido)-1-oxoisoindoline-4-carboxylic acid
  • Figure US20160311772A1-20161027-C00413
  • To a suspension solution of compound 51 (5.0 g, 14.3 mmol), KOAc (5.6 g, 57.2 mmol), KI (2.4 g, 14.3 mmol), Pd(OAc)2 (321 mg, 1.43 mmol) and PPh3 (750 mg, 2.86 mmol) in DMF (125 mL) and H2O (7.5 mL) was purged with CO and stirred at 100° C. for 8 hours. The reaction mixture was concentrated in vacuo, added with H2O (400 mL) and adjusted to pH 8 by adding 1M NaOH solution. The suspension solution was filtered through a Celite pad; the filtrate was washed with EtOAc (100 mL×3); and the aqueous phase was partially concentrated with water and acidified to pH 4 with 10% HCl solution. The precipitate thus obtained was collected to give the title compound 55 (1.6 g) as a white solid.
  • 1H NMR (400 MHz, DMSO-d6) δ 13.15 (s, 1H), 11.81 (s, 1H), 9.13 (s, 1H), 8.53-8.51 (d, J=8.6 Hz, 1H), 8.15-8.13 (d, J=8.6 Hz, 1H), 8.05-8.01 (m, 2H), 7.49-7.44 (d, J=8.8 Hz, 2H), 4.64 (s, 2H); [M+H]−313.0.
    • Example 389 7-(4-Fluorobenzamido)-N-methyl-1-oxoisoindoline-4-carboxamide
  • Figure US20160311772A1-20161027-C00414
  • To a suspension solution of 7-(4-fluorobenzamido)-1-oxoisoindoline-4-carboxylic acid 55 (100 mg, 0.32 mmol) and MeNH2HCl (33 mg, 0.48 mmol) in CH2Cl2 (1.6 mL) was added EDCI (92 mg, 0.48 mmol), HOBt (86 mg, 0.64 mmol) and NMM (0.1 mL, 0.95 mmol). The resulting mixture was purged with nitrogen, and stirred at room temperature for 12 hours. The reaction mixture was then cooled to room temperature, diluted with EtOAc (100 mL) and water (100 mL), and then filtered. The filtrate was washed with brine (200 mL), and the organic phase was concentrated in vacuo and purified by column chromatography to give the title compound 56 (84.1 mg, 80%).
  • 1H NMR (400 MHz, DMSO-d6) δ 11.77 (s, 1H), 9.09 (s, 1H), 8.51-8.47 (m, 2H), 8.05-8.01 (m, 3H), 7.47 (t, J=8.8 Hz, 2H), 4.66 (s, 2H), 2.79 (d, J=4.4 Hz, 3H). [M+H]+: 328.
  • The following compounds of Examples 390 to 392 were obtained by using corresponding starting materials and repeating the procedure of Example 389.
    • Example 390 N-methyl-1-oxo-7-(4-((2-(pyrrolidin-1-yl)ethyl)amino) benzamido)isoindoline-4-carboxamide
  • Figure US20160311772A1-20161027-C00415
  • 1H NMR (400 MHz, DMSO-d6) δ 11.54 (s, 1H), 9.01 (s, 1H), 8.50-8.45 (m, 2H), 7.98 (d, J=8.8 Hz, 1H), 7.72 (d, J=8.8 Hz, 2H), 6.71 (d, J=8.8 Hz, 2H), 6.46 (t, J=5.2 Hz, 1H), 4.64 (s, 2H), 3.22 (q, J=6.4 Hz, 2H), 2.78 (d, J=4.4 Hz, 3H), 2.62 (t, J=6.8 Hz, 2H), 2.49-2.47 (m, 4H), 1.71-1.67 (m, 4H). [M+H]+:422.
    • Example 391 4-Fluoro-N-(3-oxo-7-(pyrrolidine-1-carbonyl)isoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00416
  • 1H NMR (400 MHz, DMSO-d6) δ 11.64 (s, 1H), 9.06 (s, 1H), 8.46 (d, J=8.4 Hz, 1H), 8.04-8.01 (m, 2H), 7.78 (d, J=8.4 Hz, 1H), 7.47 (t, J=8.4 Hz, 2H), 4.48 (s, 2H), 3.48-3.46 (m, 4H), 1.87-1.82 (m, 4H). [M+H]+: 368.
    • Example 392 N-(3-oxo-7-(pyrrolidine-1-carbonyl)isoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00417
  • 1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 8.97 (s, 1H), 8.47 (d, J=8.8 Hz, 1H), 7.73 (dd, J=8.6, 4.2 Hz, 3H), 6.71 (d, J=8.8 Hz, 2H), 6.45 (t, J=5.2 Hz, 1H), 4.46 (s, 2H), 3.48-3.44 (m, 4H), 3.30-3.22 (m, 4H), 2.65-2.63 (m, 2H), 1.86-1.83 (m, 4H), 1.72-1.68 (m, 4H). [M+H]+:462.
    • Example 393 4-Fluoro-N-(7-(2-hydroxypropan-2-yl)-3-oxoisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00418
    • Step 1: Preparation of methyl 7-(4-fluorobenzamido)-1-oxoisoindoline-4-carboxylate (57)
  • Figure US20160311772A1-20161027-C00419
  • To a suspension solution of 7-(4-fluorobenzamido)-1-oxoisoindoline-4-carboxylic acid 55 (100 mg, 0.32 mmol) in CH2Cl2 (1.6 mL) was added TMS dizaomethane (0.25 mL, 0.48 mmol). The resulting mixture was purged with nitrogen, and stirred at room temperature for 12 hours. The reaction mixture was cooled to room temperature, diluted with EtOAc (100 mL) and water (100 mL), and then filtered. The filtrate was washed with brine (200 mL), and the organic phase was concentrated in vacuo to give the crude product 57 (140 mg) as a solid, which was directly used in the next step without further purification.
  • 1H NMR (400 MHz, DMSO-d6) δ 11.76 (s, 1H), 8.95 (s, 1H), 8.37 (d, J=8.4 Hz, 1H), 8.03-7.99 (m, 2H), 7.53 (d, J=8.4 Hz, 1H), 7.45 (t, J=8.8 Hz, 2H), 5.16 (s, 1H), 4.62 (s, 2H), 1.48 (s, 6H). [M+H]+: 329.
    • Step 2: Preparation of 4-fluoro-N-(7-(2-hydroxypropan-2-yl)-3-oxoisoindolin-4-yl)benzamide (58)
  • Figure US20160311772A1-20161027-C00420
  • To a suspension solution methyl 7-(4-fluorobenzamido)-1-oxoisoindoline-4-carboxylate 57 (140 mg, 0.32 mmol) in THF (3.2 mL) was added MeMgBr (0.5 mL, 1.60 mmol). The resulting mixture was purged with nitrogen, and stirred at room temperature for 12 hours. The reaction mixture was then cooled to room temperature, diluted with EtOAc (50 mL) and water (50 mL), filtered. The filtrate was washed with brine (50 mL), and the organic phase was concentrated in vacuo and purified by column chromatography to give the title compound 58 (61.8 mg, 59%).
  • The following compound of Example 394 was obtained by using corresponding starting materials and repeating the procedure of Example 393.
    • Example 394 N-(7-(2-hydroxypropan-2-yl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00421
  • 1H NMR (400 MHz, DMSO-d6) δ 11.51 (s, 1H), 8.86 (s, 1H), 8.38 (d, J=8.4 Hz, 1H), 7.70 (d, J=8.8 Hz, 2H), 7.47 (d, J=8.4 Hz, 1H), 6.69 (d, J=8.8 Hz, 2H), 6.37 (t, J=5.4 Hz, 1H), 5.11 (s, 1H), 4.60 (s, 2H), 3.21 (q, J=6.4 Hz, 2H), 2.62 (t, J=6.8 Hz, 2H), 2.49-2.40 (m, 4H), 1.69-1.65 (m, 5H), 1.47 (s, 6H). [M+H]+:423.
    • Example 395 N-(7-cyano-3-oxoisoindolin-4-yl)-4-fluorobenzamide
  • Figure US20160311772A1-20161027-C00422
  • A mixture of N-(7-bromo-3-oxoisoindolin-4-yl)-4-fluorobenzamide 51 (100 mg, 0.29 mmol), S-Phos (12 mg, 0.03 mmol), Zn(CN)2 (38 mg, 0.32 mmol) and Pd2(dba)3 (10 mg, 0.01 mmol) in water/DMF (2 drops/2 mL) was stirred for 45 min at 150° C. under microwave irradiation. The resulting mixture was purified by silica-gel column chromatography (Biotage flash purification system, EtOAc/Hex, KP-Sil) to give the title compound 50 (20 mg, 23%) as a white solid.
  • 1H NMR (400 MHz, DMSO-d6) δ 11.63 (br s, 1H), 9.31 (br s, 1H), 8.55 (d, J=8.4 Hz, 1H), 8.08 (d, J=8.8 Hz, 1H), 8.05-8.02 (m, 2H), 7.51-7.46 (m, 2H), 4.65 (s, 2H); [M+H]+: 296.
    • Example 396 4-Fluoro-N-(7-hydroxy-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00423
  • To a suspension solution of 4-fluoro-N-(3-oxo-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-4-yl)benzamide 60 (50 mg, 0.126 mmol) and Na2CO3 (27 mg, 0.252 mmol) in DME (0.8 mL) and H2O (0.2 mL) was added Pd(PPh3)4 (15 mg, 0.013 mmol). The resulting mixture was purged with nitrogen, and stirred at 100° C. for 12 hours. The reaction mixture was cooled to room temperature, diluted with EtOAc (100 mL) and water (100 mL), and then filtered. The filtrate was washed with brine (200 mL), and the organic phase was concentrated in vacuo and purified by column chromatography to give the title compound 61 (15 mg, 41%).
  • 1H NMR (400 MHz, DMSO-d6) δ 11.21 (s, 1H), 9.91 (s, 1H), 8.93 (s, 1H), 8.26 (d, J=8.8 Hz, 1H), 7.98 (dd, J=8.8, 5.6 Hz, 2H), 7.44 (t, J=8.8 Hz, 2H), 6.99 (d, J=8.8 Hz, 1H), 4.31 (s, 2H). [M+H]+:287.
    • Preparation Example 4 Preparation of 3,4-dihydroisoquinolin-1(2H)-one
  • Figure US20160311772A1-20161027-C00424
    Figure US20160311772A1-20161027-C00425
    • Step 1: Preparation of methyl 2-bromopentylcarbamate (63)
  • Figure US20160311772A1-20161027-C00426
  • To a stirred solution of 2-(2-bromophenyl)ethanamine (29.0 g, 144.94 mmol) in DCM (400 mL) was added pyridine (17.20 g, 217.41 mmol), which was cooled to 0° C., and then added with methyl carbonochloridate (137.7 g, 144.94 mmol) dropwise over 10 min. The reaction mixture was stirred at room temperature for 3 hours, washed with 1 M HCl (2×200 mL), H2O (200 mL) and brine, dried over Na2SO4, and then concentrated in vacuo to give the intermediate 63 (34.5 g, 133.66 mmol, 92.2%).
    • Step 2: Preparation of 5-bromo-3,4-dihydroisoquinolin-1(2H)-one (64)
  • Figure US20160311772A1-20161027-C00427
  • To a single-necked RBF filled with the intermediate 63 (34.5 g, 133.66 mmol, 1.0 eq) was added CF3SO3H (295 mL, 3341.60 mmol, 25 eq). The mixture was heated at 70° C. for 20 hours, and poured into a mixture of water and ice (3 L), adjusted to the pH of about 8 by adding NaHCO3. The mixture was extracted with EtOAc (2×1.5 L), washed with brine, dried over Na2SO4, and concentrated to give the residue, which was purified by chromatography (EtOAc:hexane=1:10˜1:1) to give the intermediate 64 (6.6 g, 29.45 mmol, 22.0%).
  • 1H NMR (400 MHz, DMSO-d6) δ 8.09 (br s, 1H), 7.88 (d, J=7.6 Hz, 1H), 7.78 (dd, J=8.0, 0.8 Hz, 1H), 7.31 (t, J=7.8 Hz, 1H), 3.40 (td, J=6.6, 2.8 Hz, 2H), 2.96 (t, J=6.6 Hz, 2H); [M+H]+: 226.
    • Step 3: Preparation of 5-bromo-8-nitro-3,4-dihydroisoquinolin-1(2H)-one (65)
  • Figure US20160311772A1-20161027-C00428
  • To a solution of the intermediate 64 (6.6 g, 29.19 mmol, 1.0 eq) in conc. H2SO4 (24 mL) was added a mixture solution of conc. HNO3 (2.4 mL) in H2SO4 (24 mL) dropwise at 0˜−5° C. over 2 hours. The resulting reaction mixture was stirred at 0˜−5° C. for 2 hours. The reaction mixture was poured into ice water (200 mL), filtered, and the filter cake was purified by chromatography (EtOAc:hexane=1:2) to give the intermediate 65 (4.9 g, 18.07 mmol, 61.9%).
  • 1H NMR (400 Hz, DMSO) δ 8.54 (s, 1H), 8.01-7.98 (d, J=8.48 Hz, 1H), 7.64-7.62 (d, J=8.48 Hz, 1H), 3.44-3.43 (m, 2H), 3.02-2.99 (t, J=6.24 Hz, 2H).
    • Step 4: Preparation of 8-nitro-5-phenyl-3,4-dihydroisoquinolin-1(2H)-one (66)
  • Figure US20160311772A1-20161027-C00429
  • A suspension solution of the intermediate 65 (800 mg, 2.95 mmol, 1.0 eq), phenylboronic acid (540 mg, 4.43 mmol), Pd(PPh3)4 (273 mg, 0.24 mmol, 0.08 eq) and Na2CO3 (625 mg, 5.90 mmol, 2.0 eq) in DME (35 mL) and H2O (9 mL) was degassed with N2 for three times, and then heated at 70° C. for 16 hours. The reaction mixture was cooled to room temperature, added with EtOAc (100 mL) and H2O (100 mL), and concentrated with EtOAc (2×100 mL) The combined organic phase was washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue thus obtained was washed with EtOAc (20 mL), and then dried to give the intermediate 66 (800 mg, 2.98 mmol).
    • Step 5: Preparation of 8-amino-5-bromo-3,4-dihydroisoquinolin-1(2H)-one (67)
  • Figure US20160311772A1-20161027-C00430
  • To a stirred solution of the intermediate 66 (800 mg, 2.98 mmol, 1.0 eq) in THF (120 mL) was added 10% Pd/C (200 mg), and the mixture was degassed with H2 three times. The mixture was heated to 40° C. and stirred for 24 hours. The reaction mixture was filtered through a Celite pad, and the filtrate was concentrated to give the intermediate 67 (560 mg, 2.35 mmol, 78.8%).
  • 1H NMR (400 MHz, DMSO-d6) δ 7.72 (br s, 1H), 7.41-7.36 (m, 2H), 7.31-7.25 (m, 3H), 7.07 (d, J=8.4 Hz, 1H), 6.94 (br s, 2H), 6.64 (d, J=8.4 Hz, 1H), 3.17-3.14 (m, 2H), 2.72 (t, J=6.2 Hz, 2H); [M+H]+: 239.
    • Step 6: Preparation of 4-fluoro-N-(1-oxo-5-phenyl-1,2,3,4-tetrahydroisoquinolin-8-yl)benzamide (68)
  • Figure US20160311772A1-20161027-C00431
  • To a solution of the intermediate 67 (560 mg, 2.35 mmol, 1.0 eq) in THF (50 mL) was added NMM (1.4 g, 0.292 mol, 6.0 eq) dropwise at room temperature. The mixture was stirred for 10 min, and then added with 4-fluorobenzoyl chloride (1.1 g, 7.05 mmol, 3.0 eq). The resulting reaction mixture was stirred at 45° C. for 3 hours, concentrated, and added with EtOAc (100 mL) and H2O (50 mL) The organic layer was washed with brine, and concentrated to give the crude product. The crude product was then filtered by chromatography to give the intermediate 68 (600 mg, 1.66 mmol, 70.6%).
  • The following compounds of Examples 397 to 400 were obtained by using corresponding starting materials and repeating the procedure of Example 396.
    • Example 397 4-Acetamido-N-(1-oxo-5-phenyl-1,2,3,4-tetrahydroisoquinolin-8-yl)benzamide
  • Figure US20160311772A1-20161027-C00432
  • 1H NMR (400 MHz, DMSO-d6) δ 13.49 (br s, 1H), 10.27 (br s, 1H), 8.73 (d, J=8.8 Hz, 1H), 8.54-8.53 (m, 1H), 8.91 (d, J=8.4 Hz, 2H), 7.77 (d, J=8.8 Hz, 2H), 7.50-7.45 (m, 3H), 7.41-7.36 (m, 3H), 3.31-3.25 (m, 2H), 2.87 (t, J=6.4 Hz, 2H), 2.10 (s, 3H); [M+H]+: 400.
    • Example 398 N-(1-oxo-5-phenyl-1,2,3,4-tetrahydroisoquinolin-8-yl) benzamide
  • Figure US20160311772A1-20161027-C00433
  • 1H NMR (400 MHz, DMSO-d6) δ 13.60 (br s, 1H), 8.75 (d, J=8.4 Hz, 1H), 8.58-8.57 (m, 1H), 7.99-7.96 (m, 2H), 7.67-7.57 (m, 3H), 7.52-7.45 (m, 3H), 7.42-7.37 (m, 3H), 3.29 (td, J=6.4, 2.8 Hz, 2H), 2.87 (t, J=6.4 Hz, 2H); [M+H]+: 343.
    • Example 399 N-(1-oxo-5-phenyl-1,2,3,4-tetrahydroisoquinolin-8-yl)furan-2-carboxamide
  • Figure US20160311772A1-20161027-C00434
  • 1H NMR (400 MHz, DMSO-d6) δ 13.46 (br s, 1H), 8.64 (d, J=8.8 Hz, 1H), 7.98-7.97 (m, 1H), 7.49-7.44 (m, 3H), 7.41-7.36 (m, 3H), 7.24 (d, J=3.6 Hz, 1H), 6.74-6.72 (m, 1H), 3.31-3.25 (m, 2H), 2.86 (t, J=6.4 Hz, 2H); [M+H]+: 333.
    • Example 400 N-(5-(2,3-dimethoxyphenyl)-1-oxo-1,2,3,4-tetrahydroisoquinolin-8-yl)-4-fluorobenzamide
  • Figure US20160311772A1-20161027-C00435
  • 1H NMR (400 MHz, DMSO-d6) δ 13.62 (br s, 1H), 8.68 (d, J=8.8 Hz, 1H), 8.55 (br s, 1H), 8.05-8.01 (m, 2H), 7.47-7.41 (m, 3H), 7.16-7.09 (m, 2H), 6.78 (dd, J=7.2, 1.6 Hz, 1H), 3.85 (s, 3H), 3.45 (s, 3H), 3.29-3.27 (m, 2H), 2.68-2.60 (m, 2H); [M+H]+: 421.
    • Example 401 N-(1-oxo-5-phenyl-1,2,3,4-tetrahydroisoquinolin-8-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00436
  • To a solution of the intermediate 68 (600 mg, 1.66 mmol, 1.0 eq) in DMAc (10 mL) was added 2-(pyrrolidin-1-yl)ethanamine (1.90 g, 16.65 mmol, 10.0 eq) and K2CO3 (1.15 g, 8.32 mmol, 5.0 eq), and the reaction mixture was stirred at 100° C. for 20 hours. The mixture was cooled to room temperature, and then added with DCM (200 mL) and H2O (100 mL) The aqueous layer was extracted with DCM (2×200 mL), washed with brine, dried over Na2SO4, and concentrated to give the crude product. The crude product was purified by prep-HPLC to give the title compound 69 (140 mg, 0.30 mmol, 18.0%).
  • 1H NMR (400 MHz, CDCl3) δ 12.94 (s, 1H), 8.90-8.88 (d, J=8.72 Hz, 1H), 7.95-7.93 (m, 2H), 7.48-7.41 (m, 3H), 7.38-7.34 (m, 1H), 7.31 (m, 2H), 6.67-6.65 (m, 2H), 6.03 (s, 1H), 4.75 (m, 1H), 3.45-3.41 (m, 2H), 3.28-3.23 (m, 2H), 2.98-2.95 (t, J=6.56 Hz, 2H), 2.77-2.74 (t, J=6.12 Hz, 2H), 2.55 (m, 4H), 1.81-1.80 (m, 4H), [M+H+]: 455.2.
  • The following compounds of Examples 402 and 403 were obtained by using corresponding starting materials and repeating the procedure of Example 401.
    • Example 402 N-(5-(2-methoxyphenyl)-1-oxo-1,2,3,4-tetrahydroisoquinolin-8-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00437
  • 1H NMR (400 MHz, CDCl3) δ 12.96 (s, 1H), 8.89-8.86 (d, J=8.68 Hz, 1H), 7.95-7.93 (m, 2H), 7.41-7.35 (m, 2H), 7.19-7.17 (m, 1H), 7.05-7.03 (m, 1H), 6.97-6.95 (d, J=8.20 Hz, 1H), 6.66-6.64 (d, J=8.64 Hz, 2H), 6.01 (s, 1H), 4.75 (m, 1H), 3.77 (s, 1H), 3.44-3.40 (m, 2H), 3.28-3.24 (m, 2H), 2.95-2.87 (m, 1H), 2.77-2.75 (t, J=6.08 Hz, 2H), 2.70-2.63 (m, 1H), 2.55 (m, 4H), 1.80 (m, 4H), M+H+485.1.
    • Example 403 N-(5-bromo-1-oxo-1,2,3,4-tetrahydroisoquinolin-8-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00438
  • 1H NMR (400 MHz, DMSO-d6) δ 13.20 (br s, 1H), 8.63 (d, J=9.2 Hz, 1H), 8.58-8.57 (m, 1H), 7.76 (d, J=9.2 Hz, 1H), 7.70 (d, J=8.8 Hz, 2H), 6.67 (d, J=8.8 Hz, 2H), 6.36 (t, J=5.4 Hz, 1H), 3.40 (td, J=6.6, 2.8 Hz, 2H), 3.20 (q, J=6.4 Hz, 2H), 3.00 (t, J=6.6 Hz, 2H), 2.61 (t, J=6.8 Hz, 2H), 1.70-1.67 (m, 4H); [M+H]+: 457.
    • Example 404 4-Fluoro-N-(3-oxo-7-(phenylthio)isoindolin-4-yl)benzamide Step 1: Preparation of 7-nitro-4-(phenylthio)isoindolin-1-one (71)
  • Figure US20160311772A1-20161027-C00439
  • To a stirred solution of benzenethiol (1.43 g, 12.97 mmol, 1.3 eq) in toluene (20 mL) was added K2CO3 (0.97 g, 7.02 mmol, 0.7 eq). The solution was degassed with N2 twice, and stirred at room temperature for 0.5 hour (as a reaction liquid A). Then a suspension solution of 4-bromo-7-nitroisoindolin-1-one 5 (2.57 g, 10.00 mmol, 1.0 eq) in toluene (30 mL) was added with Pd2(dba)3 (0.91 g, 0.99 mmol, 0.1 eq) and Xphos (0.57 g, 1.19 mmol, 0.12 eq), degassed with N2 for twice, stirred at room temperature for 10 min, and then added into the reaction liquid A, followed by stirring them at 100° C. for 20 minutes. The mixture was cooled to room temperature, and then added with EtOAc (50 mL) and H2O (50 mL) The aqueous layer was extracted with EtOAc (2×50 mL), washed with brine, dried over Na2SO4, and concentrated to give the crude product. The crude product was then purified by chromatography to give the intermediate 71 (1.10 g, 3.84 mmol, 38.4%).
  • 1H NMR (400 MHz, DMSO-d6) δ 9.08 (s, 1H), 7.89-7.83 (d, J=8.82 Hz, 1H), 7.56-7.49 (m, 5H), 7.31-7.29 (d, J=8.32 Hz, 1H), 4.34 (s, 2H).
    • Step 2: Preparation of 7-amino-4-(phenylthio)isoindolin-1-one (72)
  • Figure US20160311772A1-20161027-C00440
  • To a stirred solution of the intermediate 71 (1.1 g, 3.84 mmol, 1.0 eq) in THF (190 mL) was added 10% Pd/C (700 mg). The mixture was degassed with H2 three times, heated to 40° C. and stirred for 24 hours, and filtered through a Celite pad. The filtrate was concentrated to give the intermediate 72 (650 mg, 2.53 mmol, 65.8%).
  • 1H NMR (400 MHz, DMSO-d6) δ 8.27 (s, 1H), 7.36-7.34 (d, J=8.36 Hz, 11/), 7.28-7.24 (t, J=7.60 Hz, 2H), 7.15-7.13 (t, J=7.32 Hz, 1H), 7.04-7.02 (d, J=7.48 Hz, 2H), 6.67-6.6.50 (d, J=8.36 Hz, 1H), 6.47 (s, 2H), 4.08 (s, 2H).
    • Step 3: Preparation of 4-fluoro-N-(3-oxo-7-(phenylthio)isoindolin-4-yl) benzamide (73)
  • Figure US20160311772A1-20161027-C00441
  • To a solution of the intermediate 72 (650 mg, 2.54 mmol, 1.0 eq) in THF (50 mL) was added NMM (1.5 g, 15.24 mol, 6.0 eq) dropwise at room temperature. The mixture was stirred for 10 min, added with 4-fluorobenzoyl chloride (1.2 g, 7.62 mmol, 3.0 eq), and stirred at 45° C. for 20 hours. The resulting reaction mixture was concentrated and added with EtOAc (100 mL) and H2O (50 mL) The filtrate was concentrated with EtOAc (100 mL), and the organic layer was washed with brine and concentrated. The filter cake was collected and dried to give the intermediate 73 (700 mg, 1.84 mmol, 72.4%).
    • Example 405 N-(1-oxo-5-(phenylthio)-1,2,3,4-tetrahydroisoquinolin-8-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00442
  • To a solution of the intermediate 73 (700 mg, 1.85 mmol, 1.0 eq) in DMAc (10 mL) was added 2-(pyrrolidin-1-yl)ethanamine (2.1 g, 18.50 mmol, 10.0 eq) and K2CO3 (1.3 g, 9.25 mmol, 5.0 eq), which was stirred at 100° C. for 20 hour. The resulting mixture was cooled to room temperature, and then added with DCM (200 mL) and H2O (100 mL) The aqueous layer was extracted with DCM (2×200 mL), washed with brine, dried over Na2SO4, and concentrated to crude product, which was purified by prep-HPLC to give the title compound 74 (85 mg, 0.17 mmol, 9.1%).
  • 1H NMR (400 MHz, CDCl3) δ 12.90 (s, 1H), 11.15 (s, 1H), 8.69-8.67 (d, J=8.52 Hz, 1H), 7.91-7.89 (d, J=8.64 Hz, 2H), 7.66-7.64 (d, J=8.56 Hz, 2H), 7.20-7.17 (m, 3H), 6.66-6.64 (d, J=8.68 Hz, 1H), 6.64 (s, 1H), 4.29 (s, 2H), 3.91 (s, 2H), 3.69-3.67 (m, 2H), 3.36-3.34 (m, 2H), 2.82 (s, 2H), 2.09-2.05 (m, 4H), M+H+455.2.
    • Example 406 N-(3-oxo-7-(phenylsulfonyl)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00443
  • To a solution of N-(3-oxo-7-(phenylthio)isoindolin-4-yl)benzamide 75 (0.1 g, 0.28 mmol, 1.0 eq.) in DCM (3.0 mL) was added mCPBA (0.17 g, 0.7 mmol, 2.5 eq.) at 0° C. The reaction mixture was stirred for 3 hours at room temperature and quenched with 0.5 N aqueous sodium hydrogen carbonate solution (10 mL) The resulting mixture was extracted with EtOAc (10 mL) twice, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by flash chromatography with EtOAc/n-hexane. The collected residue was triturated in 50% aqueous sodium hydrogen carbonate solution (5 mL) and then filtered to give N-(3-oxo-7-(phenylsulfonyl) isoindolin-4-yl)benzamide 76 (31 mg, 0.08 mmol, 28%) as a white solid.
  • 1H NMR (400 MHz, DMSO-d6) δ 11.84 (s, 1H), 9.30 (s, 1H), 8.66 (d, J=8.8 Hz, 1H), 8.18 (d, J=8.6 Hz, 1H), 8.01 (d, J=7.7 Hz, 2H), 7.96 (d, J=7.3 Hz, 2H), 7.72-7.60 (m, 6H), 4.68 (s, 2H); [M+H]+: 393.
  • The following compound of Example 407 was obtained by using corresponding starting materials and repeating the procedure of Example 406.
    • Example 407 N-(3-oxo-7-(phenylthio)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00444
  • 1H NMR (400 MHz, DMSO-d6) δ 11.55 (s, 1H), 9.05 (s, 1H), 8.52 (d, J=8.7 Hz, 1H), 7.97 (d, J=7.2 Hz, 2H), 7.69-7.60 (m, 5H), 7.34 (d, J=7.7 Hz, 2H), 7.25 (d, J=8.1 Hz, 3H), 4.26 (s, 2H); [M+H]+: 361.
    • Example 408 4-Fluoro-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00445
  • A mixture of intermediate 51 (3.0 g, 8.60 mmol, 1.0 eq.), aniline (2.4 g, 25.80 mmol, 3.0 eq.), Pd2dba3 (0.39 g, 5 mol %), BrettPhos (0.46 g, 10 mol %) and K3PO4 (9.1 g, 43.0 mmol, 5.0 eq.) was suspended in a solution of dioxane/water (10:1, 100 mL, 0.1 M). The resulting mixture was stirred at 100° C. for 15 hours and cooled to room temperature. The reaction mixture was diluted in acetone (300 mL) and SMOPEX-234TM (3.0 g), and then added with MgSO4 (20 g). After stirring them for 3 hours, the resultant was filtered through a plug of Celite and concentrated. The residual mixture was triturated in MeOH (30 mL) twice, and filtered to give the precipitate 77 (2.2 g, 6.1 mmol, 71%) as a yellow solid.
  • 1H NMR (400 MHz, DMSO-d6) δ 11.34 (s, 1H), 8.93 (s, 1H), 8.35 (d, J=8.7 Hz, 1H), 8.04-7.96 (m, 2H), 7.91 (s, 1H), 7.44 (q, J=9.0 Hz, 1H), 7.25 (t, J=7.8 Hz, 1H), 7.01 (d, J=7.6 Hz, 1H), 6.85 (t, J=7.3 Hz, 1H), 4.31 (s, 2H); MS (ESI) m/z 362 (M+H)+.
  • The following compounds of Examples 409 to 437 were obtained by using corresponding starting materials and repeating the procedure of Example 408.
    • Example 409 N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00446
  • 1H NMR (400 MHz, DMSO-d6) δ 11.37 (s, 1H), 8.89 (s, 1H), 8.38 (d, J=8.8 Hz, 1H), 7.95 (d, J=7.0 Hz, 2H), 7.88 (s, 1H), 7.65-7.58 (m, 3H), 7.41 (d, J=8.8 Hz, 2H), 7.25 (t, J=7.8 Hz, 2H), 7.01 (d, J=7.8 Hz, 2H), 6.95 (t, J=7.1 Hz, 1H), 4.31 (s, 2H); [M+H]+: 344.
    • Example 410 N-(7-((2-methoxyphenyl)amino)-3-oxoisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00447
  • 1H NMR (400 MHz, DMSO-d6) δ 11.38 (s, 1H), 8.89 (s, 1H), 8.35 (d, J=8.7 Hz, 1H), 7.94 (d, J=6.9 Hz, 2H), 7.66-7.58 (m, 3H), 7.20 (s, 1H), 7.16 (d, J=8.8 Hz, 1H), 7.02 (d, J=8.0 Hz, 1H), 6.94-6.83 (m, 4H), 4.30 (s, 2H), 3.81 (s, 3H); [M+H]+: 374.
    • Example 411 N-(3-oxo-7-(o-tolylamino)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00448
  • 1H NMR (400 MHz, DMSO-d6) δ 11.35 (s, 1H), 8.88 (s, 1H), 8.33 (d, J=8.6 Hz, 1H), 7.93 (d, J=6.6 Hz, 2H), 7.64-7.59 (m, 3H), 7.28 (s, 1H), 7.21 (d, J=8.4 Hz, 1H), 7.12 (t, J=7.2 Hz, 1H), 6.94 (dd, J=12.2, 9.1 Hz, 3H) 4.20 (s, 2H), 2.20 (s, 3H); [M+H]+: 358.
    • Example 412 N-(3-oxo-7-(p-tolylamino)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00449
  • 1H NMR (400 MHz, DMSO-d6) δ 11.35 (s, 1H), 8.91 (s, 1H), 8.35 (d, J=8.6 Hz, 1H), 7.94 (d, J=6.7 Hz, 2H), 7.76 (s, 1H), 7.64-7.58 (m, 3H), 7.33 (d, J=8.8 Hz, 1H), 7.08 (d, J=8.0 Hz, 2H), 6.95 (d, J=8.3 Hz, 2H), 4.29 (s, 2H), 2.24 (s, 3H); [M+H]+: 358.
    • Example 413 N-(7-((2-fluorophenyl)amino)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00450
  • 1H NMR (400 MHz, DMSO-d6) δ 11.39 (s, 1H), 8.93 (s, 1H), 8.35 (d, J=8.7 Hz, 1H), 7.95 (d, J=6.8 Hz, 2H), 7.76 (s, 1H), 7.67-7.58 (m, 3H), 7.25-7.16 (m, 2H), 7.11-7.04 (m, 2H), 6.97-6.92 (m, 1H), 4.32 (s, 2H); [M+H]+: 362.
    • Example 414 N-(7-((4-fluorophenyl)amino)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00451
  • 1H NMR (400 MHz, DMSO-d6) δ 11.36 (s, 1H), 8.93 (s, 1H), 8.37 (d, J=8.7 Hz, 1H), 7.94 (d, J=6.7 Hz, 2H), 7.87 (s, 1H), 7.65-7.58 (m, 3H), 7.33 (d, J=8.7 Hz, 1H), 7.12-7.01 (m, 4H), 4.30 (s, 2H); [M+H]+: 362.
    • Example 415 N-(7-((3-fluorophenyl)amino)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00452
  • 1H NMR (400 MHz, DMSO-d6) δ 11.41 (s, 1H), 8.95 (s, 1H), 8.43 (d, J=8.8 Hz, 1H), 8.17 (s, 1H), 7.95 (d, J=6.8 Hz, 2H), 7.68-7.59 (m, 3H), 7.48 (d, J=8.8 Hz, 1H), 7.24 (q, J=8.0 Hz, 1H), 6.79 (d, J=7.6 Hz, 1H), 6.71 (d, J=11.8 Hz, 1H), 6.60-6.57 (m, 1H), 4.32 (s, 2H); [M+H]+: 362.
    • Example 416 N-(7-((4-methoxyphenyl)amino)-3-oxoisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00453
  • 1H NMR (400 MHz, DMSO-d6) δ 11.38 (s, 1H), 8.92 (s, 1H), 8.39 (d, J=8.8 Hz, 1H), 7.93 (dd, J=8.0, 6.4 Hz, 3H), 7.65-7.58 (m, 3H), 7.45 (d, J=8.7 Hz, 1H), 7.14 (t, J=8.1 Hz, 1H), 6.59 (d, J=8.0 Hz, 1H), 6.54 (t, J=2.1 Hz, 1H), 6.43 (dd, J=8.3, 1.8 Hz, 1H), 4.32 (s, 2H), 3.71 (s, 3H); [M+H]+: 374.
    • Example 417 4-Methyl-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00454
  • 1H NMR (400 MHz, DMSO-d6) δ 11.99 (s, 1H), 8.66 (s, 1H), 8.47 (d, J=8.6 Hz, 1H), 7.86 (s, 1H), 7.72 (d, J=8.6 Hz, 2H), 7.37 (d, J=3.3 Hz, 1H), 7.23 (t, J=8.0 Hz, 2H), 6.97 (d, J=8.0 Hz, 2H), 6.82 (t, J=7.3 Hz, 1H), 6.70 (d, J=8.9 Hz, 2H), 4.29 (s, 2H), 3.25 (s, 3H); [M+H]+: 358.
    • Example 418 N-(7-((3-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-fluorobenzamide
  • Figure US20160311772A1-20161027-C00455
  • MS (ESI) m/z 396 (M+H)+.
  • 1H NMR (400 MHz, DMSO-d6) δ 11.36 (s, 1H), 8.97 (s, 1H), 8.38 (d, J=8.8 Hz, 1H), 8.15 (s, 1H), 8.01-7.97 (m, 2H), 7.46-7.42 (m, 3H), 7.22 (t, J=8.0 Hz, 1H), 6.93-6.89 (m, 2H), 6.83-8.61 (m, 1H), 4.30 (s, 2H); [M+H]+: 396.
    • Example 419 N-(7-((2-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-fluorobenzamide
  • Figure US20160311772A1-20161027-C00456
  • MS (ESI) m/z 396 (M+H)+.
  • 1H NMR (400 MHz, DMSO-d6) δ 11.40 (s, 1H), 8.95 (s, 1H), 8.37 (d, J=8.4 Hz, 1H), 8.02-7.97 (m, 2H), 7.58 (s, 1H), 7.47-7.40 (m, 3H), 7.24 (d, J=8.8 Hz, 1H), 7.20-7.15 (m, 1H), 6.91-6.89 (m, 2H), 4.24 (s, 2H); [M+H]+: 396.
    • Example 420 2-Fluoro-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00457
  • 1H NMR (400 MHz, DMSO-d6) δ 11.21 (d, J=6.8 Hz, 1H), 8.83 (s, 1H), 8.44 (d, J=8.7 Hz, 1H), 8.00-7.89 (m, 2H), 7.69-7.62 (m, 1H), 7.47-7.35 (m, 3H), 7.26 (t, J=7.7 Hz, 1H), 7.03 (d, J=7.8 Hz, 1H), 6.86 (t, J=7.2 Hz, 1H), 4.31 (s, 2H); MS (ESI) m/z 362 (M+H)+.
    • Example 421 3-Fluoro-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00458
  • 1H NMR (400 MHz, DMSO-d6) δ 11.38 (s, 1H), 8.95 (s, 1H), 8.34 (d, J=8.7 Hz, 1H), 7.93 (s, 1H), 7.78 (d, J=7.9 Hz, 1H), 7.79-7.66 (m, 2H), 7.53-7.50 (m, 1H), 7.42 (d, J=8.7 Hz, 1H), 7.26 (t, J=7.9 Hz, 2H), 7.02 (d, J=7.6 Hz, 2H), 6.86 (t, J=7.3 Hz, 1H), 4.32 (s, 2H); MS (ESI) m/z 362 (M+H)+.
    • Example 422 N-(7-((2,3-dimethoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-fluorobenzamide
  • Figure US20160311772A1-20161027-C00459
  • 1H NMR (400 MHz, DMSO-d6) δ 11.37 (s, 1H), 8.93 (s, 1H), 8.35 (d, J=8.6 Hz, 1H), 8.00 (dd, J=8.8, 5.3 Hz, 2H), 7.45 (t, J=8.8 Hz, 2H), 7.37 (s, 1H), 7.28 (d, J=8.7 Hz, 1H), 6.90 (t, J=8.2 Hz, 1H), 6.58 (d, J=8.4 Hz, 1H), 6.51 (d, J=8.2 Hz, 1H), 4.31 (s, 2H), 3.80 (s, 3H), 3.69 (s, 3H); [M+H]+: 422.
    • Example 423 N-(7-((3,5-bis(trifluoromethyl)phenyl)amino)-3-oxoisoindolin-4-yl)-4-fluorobenzamide
  • Figure US20160311772A1-20161027-C00460
  • 1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 9.04 (s, 1H), 8.76 (s, 1H), 8.46 (d, J=8.6 Hz, 1H), 8.01 (d, J=5.4 Hz, 2H), 7.58 (d, J=7.4 Hz, 1H), 7.47-7.37 (m, 5H), 4.34 (s, 2H); [M+H]+: 498.
    • Example 424 N-(7-((2,3-dimethylphenyl)amino)-3-oxoisoindolin-4-yl)-4-fluorobenzamide
  • Figure US20160311772A1-20161027-C00461
  • 1H NMR (400 MHz, DMSO-d6) δ 11.30 (s, 1H), 8.90 (s, 1H), 8.25 (d, J=8.7 Hz, 1H), 7.98 (dd, J=8.8, 5.4 Hz, 2H), 7.44 (t, J=8.9 Hz, 3H), 7.36 (s, 1H), 6.91 (d, J=7.5 Hz, 1H), 6.84 (d, J=7.8 Hz, 1H), 6.77 (d, J=8.7 Hz, 1H), 4.21 (s, 2H), 2.27 (s, 3H), 2.08 (s, 3H); [M+H]+: 390.
    • Example 425 4-Fluoro-N-(7-((2-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00462
  • 1H NMR (400 MHz, DMSO-d6) δ 11.35 (s, 1H), 8.93 (s, 1H), 8.31 (d, J=8.7 Hz, 1H), 8.0 (dd, J=8.8, 5.4 Hz, 2H), 7.45 (t, J=8.8 Hz, 2H), 7.24 (s, 1H), 7.15 (d, J=8.7 Hz, 1H), 7.02 (d, J=6.8 Hz, 1H), 6.95-6.83 (m, 3H), 4.30 (s, 2H), 3.81 (s, 3H); [M+H]+: 392.
    • Example 426 4-Fluoro-N-(3-oxo-7-(o-tolylamino)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00463
  • 1H NMR (400 MHz, DMSO-d6) δ 11.34 (s, 1H), 8.92 (s, 1H), 8.30 (d, J=8.7 Hz, 1H), 7.99 (dd, J=8.8, 5.4 Hz, 2H), 7.45 (t, J=8.8 Hz, 3H), 7.30 (s, 1H), 7.21 (d, J=7.1 Hz, 1H), 7.12 (t, J=7.5 Hz, 1H), 6.94 (t, J=8.4 Hz, 3H), 4.21 (s, 2H), 2.20 (s, 3H); [M+H]+: 376.
    • Example 427 4-Fluoro-N-(3-oxo-7-(pyridin-3-ylamino)isoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00464
  • 1H NMR (400 MHz, DMSO-d6) δ 11.37 (s, 1H), 8.98 (s, 1H), 8.38 (d, J=8.6 Hz, 1H), 8.32 (d, J=2.7 Hz, 1H), 8.13 (s, 1H), 8.05 (dd, J=4.6, 1.3 Hz, 1H), 8.02-7.99 (m, 2H), 7.48-7.43 (m, 3H), 7.38-7.35 (m, 1H), 7.26-7.23 (m, 1H), 4.33 (s, 2H); [M+H]+: 363.
    • Example 428 4-Fluoro-N-(3-oxo-7-(pyridin-2-ylamino)isoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00465
  • 1H NMR (400 MHz, DMSO-d6) δ 11.42 (s, 1H), 8.95 (s, 1H), 8.67 (s, 1H), 8.38 (d, J=8.8 Hz, 1H), 8.13 (d, J=3.7 Hz, 1H), 8.06 (d, J=8.7 Hz, 1H), 8.01 (dd, J=8.8, 5.4 Hz, 3H), 7.61-7.57 (m, 1H), 7.45 (t, J=8.8 Hz, 2H), 6.89 (d, J=8.4 Hz, 1H), 6.76 (d, J=6.0 Hz, 1H), 4.40 (s, 2H); [M+H]+: 363.
    • Example 429 4-Fluoro-N-(3-oxo-7-(pyrazin-2-ylamino)isoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00466
  • 1H NMR (400 MHz, DMSO-d6) δ 11.44 (s, 1H), 9.12 (s, 1H), 9.00 (s, 1H), 8.41 (d, J=8.8 Hz, 1H), 8.30 (d, J=1.2 Hz, 1H), 8.12-8.11 (m, 1H), 8.06-8.00 (m, 4H), 7.95 (d, J=2.3 Hz, 1H), 7.46 (t, J=8.8 Hz, 3H), 4.42 (s, 2H); [M+H]+: 364.
    • Example 430 4-Fluoro-N-(7-(1-methyl-1H-pyrazol-4-yl)amino)-3-oxoisoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00467
  • 1H NMR (400 MHz, DMSO-d6) δ 11.22 (s, 1H), 8.89 (s, 1H), 8.25 (d, J=8.7 Hz, 1H), 7.99-7.95 (m, 3H), 7.70 (s, 1H), 7.48-7.39 (m, 4H), 7.35 (d, J=6.0 Hz, 2H), 6.97 (d, J=8.7 Hz, 1H), 4.27 (s, 2H), 3.82 (s, 3H); [M+H]+: 366.
    • Example 431 N-(7-((3-methoxyphenyl)amino)-3-oxoisoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00468
  • 1H NMR (400 MHz, DMSO-d6) δ 11.38 (s, 1H), 8.92 (s, 1H), 8.39 (d, J=8.8 Hz, 1H), 7.94 (dd, J=8.0, 6.4 Hz, 3H), 7.65-7.58 (m, 3H), 7.45 (d, J=8.7 Hz, 1H), 7.14 (t, J=8.1 Hz, 1H), 6.54 (t, J=2.4 Hz, 1H), 6.43 (dd, J=8.3, 1.8 Hz, 1H), 4.32 (s, 2H), 3.71 (s, 3H); [M+H]+: 374.
    • Example 432 2-Methoxy-N-(3-oxo-7-(phenylamino)isoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00469
  • 1H NMR (400 MHz, DMSO-d6) δ 11.92 (s, 1H), 8.71 (s, 1H), 8.62 (d, J=8.9 Hz, 1H), 8.05 (dd, J=7.8, 1.7 Hz, 1H), 7.84 (s, 1H), 7.60-7.55 (m, 1H), 7.39 (d, J=8.8 Hz, 1H), 7.24 (t, J=7.8 Hz, 1H), 7.12 (t, J=7.5 Hz, 1H), 7.01 (d, J=7.6 Hz, 1H), 6.84 (t, J=7.3 Hz, 1H), 4.28 (s, 2H), 4.05 (s, 3H); [M+H]+: 374.
    • Example 433 4-Methoxy-N-(3-oxo-7-(phenylamino)isoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00470
  • 1H NMR (400 MHz, DMSO-d6) δ 11.29 (s, 1H), 8.91 (s, 1H), 8.37 (d, J=8.7 Hz, 1H), 7.92-7.88 (m, 3H), 7.40 (d, J=8.8 Hz, 1H), 7.24 (t, J=7.9 Hz, 2H), 7.13 (d, J=8.8 Hz, 2H), 7.00 (d, J=7.6 Hz, 2H), 6.84 (t, J=7.3 Hz, 1H), 4.31 (s, 2H), 3.85 (s, 3H); [M+H]+: 374.
    • Example 434 3-Methoxy-N-(3-oxo-7-(phenylamino)isoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00471
  • 1H NMR (400 MHz, DMSO-d6) δ 11.37 (s, 1H), 8.92 (s, 1H), 8.36 (d, J=8.7 Hz, 1H), 7.91 (s, 1H), 7.54-7.47 (m, 3H), 7.41 (d, J=8.7 Hz, 1H), 7.27-7.20 (m, 3H), 7.01 (d, J=7.6 Hz, 2H), 6.85 (t, J=7.3 Hz, 1H), 4.31 (s, 2H), 3.85 (s, 3H); [M+H]+: 374.
    • Example 435 4-Acetamido-N-(3-oxo-7-(phenylamino)isoindolin-4-yl) benzamide
  • Figure US20160311772A1-20161027-C00472
  • 1H NMR (400 MHz, DMSO-d6) δ 11.30 (s, 1H), 10.29 (s, 1H), 8.91 (s, 1H), 8.37 (d, J=8.9 Hz, 1H), 7.88 (d, J=8.1 Hz, 3H), 7.77 (d, J=8.8 Hz, 2H), 7.40 (d, J=9.0 Hz, 1H), 7.24 (d, J=7.9 Hz, 2H), 7.00 (d, J=7.6 Hz, 2H), 6.84 (t, J=7.2 Hz, 1H), 4.31 (s, 2H), 2.09 (s, 3H); [M+H]+: 401.
    • Example 436 N-(3-oxo-7-(m-tolylamino)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00473
  • 1H NMR (400 MHz, DMSO-d6) δ 11.37 (s, 1H), 8.92 (s, 1H), 8.38 (d, J=8.6 Hz, 1H), 7.94 (d, J=8.3 Hz, 2H), 7.83 (s, 1H), 7.64-7.58 (m, 3H), 7.40 (d, J=8.7 Hz, 1H), 7.13 (t, J=7.6 Hz, 1H), 6.81 (d, J=11.4 Hz, 2H), 6.67 (d, J=8.0 Hz, 1H), 4.30 (s, 2H), 2.25 (s, 3H); [M+H]+: 358.
    • Example 437 N-(7-(1H-pyrazol-3-yl)amino)-3-oxoisoindolin-4-yl)-4-fluorobenzamide
  • Figure US20160311772A1-20161027-C00474
  • 1H NMR (400 MHz, DMSO-d6) δ 12.91 (s, 1H), 10.33 (s, 1H), 7.82 (dd, J=7.6, 1.6 Hz, 1H), 7.76 (d, J=7.4 Hz, 2H), 7.54 (t, J=8.4 Hz, 1H), 7.46 (t, J=7.0 Hz, 2H), 7.36 (d, J=7.2 Hz, 1H), 7.22 (d, J=8.3 Hz, 1H), 7.10 (t, J=7.5 Hz, 1H), 7.04 (br s, 1H), 3.97 (s, 2H); [M+H]+: 352.
    • Example 438 N-(3-oxo-7-(phenylamino)isoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00475
  • A mixture of the intermediate 77 (0.1 g. 0.27 mmol, 1.0 eq.) and 1-(2-aminoethyl)pyrrolidine (0.14 g, 1.1 mmol, 4.0 eq.) was placed in a sealed tube and stirred at 160° C. for 15 hours. The resulting mixture was cooled to room temperature and diluted in DCM (1 mL) The diluted solution was added into hexane (5 mL) with vigorous stirring. The mixture thus obtained was filtered to give the precipitate 78 (0.12 g, 0.26 mmol, 96%) as a yellow solid.
  • 1H NMR (400 MHz, DMSO-d6) δ 11.13 (s, 1H), 8.87 (s, 1H), 8.38 (d, J=8.8 Hz, 1H), 7.85 (s, 1H), 7.69 (d, J=8.8 Hz, 2H), 7.38 (d, J=8.8 Hz, 1H), 7.23 (d, J=7.8 Hz, 2H), 6.97 (d, J=8.8 Hz, 2H), 6.82 (t, J=7.2 Hz, 1H), 6.69 (d, J=8.8 Hz, 2H), 6.35 (t, J=5.2 Hz, 1H), 4.29 (s, 2H), 3.21 (q, J=6.4 Hz, 2H), 2.62 (t, J=6.8 Hz, 2H), 2.50-2.48 (m, 6H), 1.72-1.68 (m, 4H). [M+H]+: 456.
  • The following compounds of Examples 439 to 492 were obtained by using corresponding starting materials and repeating the procedure of Example 438.
    • Example 439 N-(3-oxo-7-(phenylamino)isoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00476
  • 1H NMR (400 MHz, DMSO-d6) δ 11.13 (s, 1H), 8.87 (s, 1H), 8.38 (d, J=8.7 Hz, 1H), 7.85 (s, 1H), 7.69 (d, J=8.3 Hz, 2H), 7.38 (d, J=8.7 Hz, 1H), 7.23 (t, J=7.9 Hz, 2H), 6.97 (d, J=7.7 Hz, 2H), 6.82 (t, J=7.3 Hz, 1H), 6.69 (d, J=8.8 Hz, 2H), 6.27 (t, J=5.3 Hz, 1H), 4.29 (s, 2H), 3.20 (q, J=6.3 Hz, 2H), 2.45-2.33 (m, 6H), 1.58-1.44 (m, 4H), 1.41-1.30 (m, 2H); MS (ESI) m/z 470 (M+H)+.
    • Example 440 N-(3-oxo-7-(phenylamino)isoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide hydrochloride
  • Figure US20160311772A1-20161027-C00477
  • 1H NMR (400 MHz, DMSO-d6) δ 11.16 (s, 1H), 9.98 (br s, 1H), 8.88 (s, 1H), 8.36 (d, J=8.8 Hz, 1H), 7.73 (d, J=8.8 Hz, 2H), 7.38 (d, J=8.8 Hz, 1H), 7.22 (t, J=8.0 Hz, 2H), 6.97 (d, J=7.6 Hz, 2H), 6.81 (t, J=7.2 Hz, 1H), 6.76 (d, J=8.4 Hz, 2H), 4.95 (br s, 1H), 4.29 (s, 2H), 3.55 (t, J=6.4 Hz, 2H), 3.50-3.47 (m, 2H), 3.22-3.18 (m, 2H), 2.93-2.90 (m, 2H), 1.78-1.68 (m, 5H), 1.38-1.34 (m, 1H); MS (ESI) m/z 470 (M+H)+.
    • Example 441 4-((2-(Dimethylamino)ethyl)amino)-N-(3-oxo-7-phenylamino) isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00478
  • 1H NMR (400 MHz, DMSO-d6) δ 11.18 (s, 1H), 8.88 (s, 1H), 8.39 (d, J=8.7 Hz, 1H), 7.85 (s, 1H), 7.77 (d, J=8.3 Hz, 2H), 7.39 (d, J=8.8 Hz, 1H), 7.24 (t, J=7.9 Hz, 2H), 6.98 (d, J=7.8 Hz, 2H), 6.86-6.78 (m, 3H), 4.29 (s, 2H), 3.52-3.44 (m, 2H), 3.01 (s, 3H), 2.68-2.59 (m, 2H), 2.30 (s, 3H); MS (ESI) m/z 430 (M+H)+.
    • Example 442 4-((2-Morpholinoethyl)amino)-N-(3-oxo-7-(phenylamino) isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00479
  • 1H NMR (400 MHz, DMSO-d6) δ 11.12 (s, 1H), 8.86 (s, 1H), 8.37 (d, J=8.8 Hz, 1H), 7.84 (s, 1H), 7.68 (d, J=8.8 Hz, 2H), 7.37 (d, J=8.8 Hz, 1H), 7.22 (t, J=7.9 Hz, 2H), 6.96 (d, J=7.7 Hz, 2H), 6.80 (t, J=7.3 Hz, 1H), 6.69 (d, J=8.8 Hz, 2H), 6.30 (t, J=5.3 Hz, 1H), 4.28 (s, 2H), 3.62-3.53 (m, 5H), 3.25-3.15 (m, 2H), 2.51-2.40 (m, 5H); MS (ESI) m/z 472 (M+H)+.
    • Example 443 4-((2-(4-Methylpiperazin-1-yl)ethyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00480
  • 1H NMR (400 MHz, DMSO-d6) δ 11.13 (s, 1H), 8.86 (s, 1H), 8.37 (d, J=8.7 Hz, 1H), 7.84 (s, 1H), 7.68 (d, J=8.7 Hz, 2H), 7.38 (d, J=8.7 Hz, 1H), 7.24 (t, J=7.9 Hz, 2H), 6.96 (d, J=7.7 Hz, 2H), 6.82 (t, J=7.3 Hz, 1H), 6.68 (d, J=8.8 Hz, 2H), 6.27 (t, J=5.2 Hz, 1H), 4.28 (s, 2H), 3.25-3.13 (m, 4H), 2.69-2.59 (m, 2H), 2.37-2.17 (m, 6H), 2.13 (s, 3H); MS (ESI) m/z 470 (M+H)+.
    • Example 444 4-((2-Methoxyethyl)amino)-N-(3-oxo-7-(phenylamino) isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00481
  • 1H NMR (400 MHz, DMSO-d6) δ 11.12 (s, 1H), 8.88 (s, 1H), 8.36 (d, J=8.8 Hz, 1H), 7.85 (s, 1H), 7.67 (d, J=8.7 Hz, 2H), 7.36 (d, J=8.7 Hz, 1H), 7.22 (t, J=7.9 Hz, 2H), 6.96 (d, J=7.7 Hz, 2H), 6.81 (t, J=7.3 Hz, 1H), 6.68 (d, J=8.8 Hz, 2H), 6.48 (t, J=5.5 Hz, 1H), 4.28 (s, 2H), 3.49 (t, J=5.5 Hz, 2H), 3.31-3.22 (m, 5H); MS (ESI) m/z 417 (M+H)+.
    • Example 445 N-(7-((3-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00482
  • 1H NMR (400 MHz, DMSO-d6) δ 11.12 (s, 1H), 8.87 (s, 1H), 8.38 (d, J=8.7 Hz, 1H), 7.85 (s, 1H), 7.68 (d, J=8.6 Hz, 2H), 7.39 (d, J=8.7 Hz, 1H), 7.11 (t, J=7.9 Hz, 1H), 6.68 (d, J=8.7 Hz, 3H), 6.53 (d, J=8.1 Hz, 1H), 6.49 (s, 1H), 6.41-6.31 (m, 2H), 4.29 (s, 2H), 3.34 (s, 3H), 3.25-3.14 (m, 3H), 2.63-2.55 (m, 3H), 1.19-1.10 (m, 6H); MS (ESI) m/z 486 (M+H)+.
    • Example 446 N-(7-((3-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00483
  • 1H NMR (400 MHz, DMSO-d6) δ 11.12 (s, 1H), 8.87 (s, 1H), 8.37 (d, J=8.7 Hz, 1H), 7.86 (s, 1H), 7.68 (d, J=8.7 Hz, 3H), 7.39 (d, J=8.7 Hz, 1H), 7.11 (t, J=7.9 Hz, 1H), 6.68 (d, J=8.7 Hz, 3H), 6.53 (d, J=8.1 Hz, 1H), 6.49 (d, J=2.1 Hz, 1H), 6.41-6.35 (m, 1H), 6.31-6.23 (m, 1H), 4.29 (s, 2H), 3.69 (s, 3H), 3.23-3.14 (m, 3H), 2.41-2.29 (m, 3H), 1.53-1.43 (m, 6H), 1.39-1.25 (m, 3H); MS (ESI) m/z 500 (M+H)+.
    • Example 447 N-(7-((3-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00484
  • 1H NMR (400 MHz, DMSO-d6) δ 11.12 (s, 1H), 8.87 (s, 1H), 8.37 (d, J=8.7 Hz, 1H), 7.85 (s, 1H), 7.68 (d, J=8.7 Hz, 2H), 7.39 (d, J=8.7 Hz, 1H), 7.11 (t, J=7.9 Hz, 1H), 6.64 (d, J=8.7 Hz, 3H), 6.53 (d, J=8.1 Hz, 1H), 6.48 (d, J=6.0 Hz, 2H), 6.41-6.31 (m, 1H), 4.28 (s, 2H), 3.71 (s, 3H), 3.15-3.07 (m, 2H), 2.43-2.31 (m, 4H), 1.75-1.59 (m, 8H); MS (ESI) m/z 500 (M+H)+.
    • Example 448 N-(7-(3-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00485
  • 1H NMR (400 MHz, DMSO-d6) δ 11.12 (s, 1H), 8.87 (s, 1H), 8.37 (d, J=8.7 Hz, 1H), 7.85 (s, 1H), 7.68 (d, J=8.7 Hz, 3H), 7.40 (d, J=8.8 Hz, 1H), 7.11 (t, J=8.1 Hz, 1H), 6.68 (d, J=8.7 Hz, 3H), 6.64 (d, J=8.8 Hz, 1H), 6.57-6.43 (m, 3H), 6.39 (dd, J=8.1, 2.1 Hz, 1H), 4.29 (s, 2H), 3.69 (s, 3H), 3.15-3.04 (m, 3H), 2.38-2.20 (m, 4H), 1.53-1.43 (m, 6H), 1.39-1.25 (m, 3H); MS (ESI) m/z 514 (M+H)+.
    • Example 449 N-(3-oxo-7-(m-tolylamino)isoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00486
  • 1H NMR (400 MHz, DMSO-d6) δ 11.12 (s, 1H), 8.86 (s, 1H), 8.36 (d, J=8.7 Hz, 1H), 7.77 (s, 1H), 7.67 (d, J=8.6 Hz, 2H), 7.35 (d, J=8.7 Hz, 1H), 7.09 (t, J=7.9 Hz, 1H), 6.75 (d, J=8.7 Hz, 2H), 6.67 (d, J=8.1 Hz, 2H), 6.63 (d, J=7.4 Hz, 1H), 6.35 (t, J=5.3 Hz, 1H), 4.26 (s, 2H), 3.35-3.14 (m, 2H), 2.60 (t, J=6.7 Hz, 2H), 2.22 (s, 3H), 1.71-1.66 (m, 6H); MS (ESI) m/z 470 (M+H)+.
    • Example 450 N-(3-oxo-7-(m-tolylamino)isoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00487
  • 1H NMR (400 MHz, DMSO-d6) δ 11.12 (s, 1H), 8.86 (s, 1H), 8.36 (d, J=8.7 Hz, 1H), 7.77 (s, 1H), 7.67 (d, J=8.6 Hz, 2H), 7.35 (d, J=8.7 Hz, 1H), 7.09 (t, J=7.9 Hz, 1H), 6.75 (d, J=8.7 Hz, 2H), 6.67 (d, J=8.1 Hz, 2H), 6.62 (d, J=7.4 Hz, 1H), 6.26 (t, J=5.3 Hz, 1H), 4.27 (s, 2H), 3.22-3.14 (m, 2H), 2.51-2.21 (m, 2H), 2.21 (s, 3H), 1.71-1.66 (m, 8H); MS (ESI) m/z 484 (M+H)+.
    • Example 451 N-(3-oxo-7-(m-tolylamino)isoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00488
  • 1H NMR (400 MHz, DMSO-d6) δ 11.11 (s, 1H), 8.86 (s, 1H), 8.36 (d, J=8.7 Hz, 1H), 7.76 (s, 1H), 7.67 (d, J=8.6 Hz, 2H), 7.35 (d, J=8.7 Hz, 1H), 7.09 (t, J=7.9 Hz, 1H), 6.79-6.71 (m, 2H), 6.67-6.59 (m, 4H), 6.48 (t, J=5.3 Hz, 1H), 4.26 (s, 2H), 3.15-3.07 (m, 2H), 2.45-2.37 (m, 2H), 2.22 (s, 3H), 1.79-1.61 (m, 8H); MS (ESI) m/z 484 (M+H)+.
    • Example 452 N-(3-oxo-7-(m-tolylamino)isoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00489
  • 1H NMR (400 MHz, DMSO-d6) δ 11.12 (s, 1H), 8.86 (s, 1H), 8.36 (d, J=8.7 Hz, 1H), 7.77 (s, 1H), 7.67 (d, J=8.6 Hz, 2H), 7.35 (d, J=8.7 Hz, 1H), 7.09 (t, J=7.9 Hz, 1H), 6.75 (d, J=8.7 Hz, 2H), 6.67 (d, J=8.1 Hz, 2H), 6.62 (d, J=7.4 Hz, 1H), 6.51 (t, J=5.3 Hz, 1H), 4.26 (s, 2H), 3.15-3.07 (m, 2H), 2.31-2.21 (m, 4H), 2.21 (s, 3H), 1.73-1.66 (m, 2H), 1.53-1.36 (m, 8H); MS (ESI) m/z 498 (M+H)+.
    • Example 453 N-(7-((2-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00490
  • 1H NMR (400 MHz, DMSO-d6) δ 11.19 (s, 1H), 8.86 (s, 1H), 8.41 (d, J=8.6 Hz, 1H), 7.69 (d, J=8.5 Hz, 2H), 7.47 (s, 1H), 7.39 (d, J=7.7 Hz, 1H), 7.24 (d, J=8.7 Hz, 1H), 7.19-7.13 (m, 1H), 6.87-6.80 (m, 2H), 6.69 (d, J=8.4 Hz, 3H), 6.39-6.31 (m, 1H), 4.22 (s, 2H), 3.25-3.15 (m, 3H), 2.68-2.59 (m, 3H), 1.77-1.61 (m, 5H); MS (ESI) m/z 490 (M+H)+.
    • Example 454 N-(7-((2-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00491
  • 1H NMR (400 MHz, DMSO-d6) δ 11.19 (s, 1H), 8.85 (s, 1H), 8.40 (d, J=8.6 Hz, 1H), 7.69 (d, J=8.5 Hz, 2H), 7.47 (s, 1H), 7.39 (d, J=7.7 Hz, 1H), 7.24 (d, J=8.7 Hz, 1H), 7.15 (t, J=7.4 Hz, 1H), 6.87-6.80 (m, 2H), 6.68 (d, J=8.7 Hz, 3H), 6.27 (t, J=5.3 Hz, 1H), 4.22 (s, 2H), 3.22-3.14 (m, 2H), 2.51-2.21 (m, 4H), 1.71-1.66 (m, 8H); MS (ESI) m/z 504 (M+H)+.
    • Example 455 N-(7-((3-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00492
  • 1H NMR (400 MHz, DMSO-d6) δ 11.19 (s, 1H), 8.86 (s, 1H), 8.41 (d, J=8.6 Hz, 1H), 8.10 (s, 1H), 7.69 (d, J=8.5 Hz, 3H), 7.47 (s, 1H), 7.40 (d, J=7.7 Hz, 2H), 7.21 (t, J=8.0 Hz, 1H), 6.91-6.75 (m, 3H), 6.38 (t, J=5.2 Hz, 1H), 4.27 (s, 2H), 3.25-3.17 (m, 3H), 2.69-2.59 (m, 3H), 1.77-1.62 (m, 5H); MS (ESI) m/z 490 (M+H)+.
    • Example 456 N-(7-((3-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00493
  • 1H NMR (400 MHz, DMSO-d6) δ 11.16 (s, 1H), 8.90 (s, 1H), 8.40 (d, J=8.6 Hz, 1H), 8.10 (s, 1H), 7.69 (d, J=8.5 Hz, 2H), 7.41 (d, J=7.7 Hz, 1H), 7.20 (t, J=8.0 Hz, 1H), 6.90-6.71 (m, 3H), 6.68 (d, J=8.3 Hz, 2H), 6.29 (t, J=5.3 Hz, 1H), 4.27 (s, 2H), 3.22-3.14 (m, 2H), 2.51-2.21 (m, 4H), 1.71-1.66 (m, 8H); MS (ESI) m/z 504 (M+H)+.
    • Example 457 N-(7-((3-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00494
  • 1H NMR (400 MHz, DMSO-d6) δ 11.15 (s, 1H), 8.88 (s, 1H), 8.41 (d, J=8.6 Hz, 1H), 8.08 (s, 1H), 7.69 (d, J=8.5 Hz, 2H), 7.40 (d, J=8.6 Hz, 1H), 7.19 (t, J=8.0 Hz, 1H), 6.91-6.74 (m, 3H), 6.65 (d, J=7.2 Hz, 3H), 6.49-6.43 (m, 1H), 4.27 (s, 2H), 3.25-3.17 (m, 3H), 2.69-2.59 (m, 3H), 1.77-1.62 (m, 7H); MS (ESI) m/z 504 (M+H)+.
    • Example 458 N-(7-((3-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00495
  • 1H NMR (400 MHz, DMSO-d6) δ 11.15 (s, 1H), 8.88 (s, 1H), 8.40 (d, J=8.6 Hz, 1H), 8.10 (s, 1H), 7.67 (d, J=8.5 Hz, 2H), 7.41 (d, J=8.6 Hz, 1H), 7.19 (t, J=8.0 Hz, 1H), 6.93-6.77 (m, 4H), 6.66 (d, J=7.2 Hz, 3H), 6.50-6.41 (m, 1H), 4.27 (s, 2H), 3.25-3.12 (m, 2H), 2.55-2.24 (m, 4H), 1.81-1.66 (m, 8H); MS (ESI) m/z 518 (M+H)+.
    • Example 459 N-(3-oxo-7-(phenylamino)isoindolin-4-yl)-4-((3-(2-oxopyrrolidin-1-yl)propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00496
  • 1H NMR (400 MHz, DMSO-d6) δ 11.12 (s, 1H), 8.87 (s, 1H), 8.37 (d, J=8.7 Hz, 1H), 7.84 (s, 1H), 7.69 (d, J=8.7 Hz, 2H), 7.37 (d, J=8.7 Hz, 1H), 7.22 (t, J=7.7 Hz, 2H), 6.95 (d, J=7.6 Hz, 3H), 6.80 (t, J=7.3 Hz, 1H), 6.55 (d, J=8.7 Hz, 2H), 6.43 (t, J=5.4 Hz, 1H), 4.28 (s, 2H), 3.31-3.05 (m, 3H), 2.15-2.07 (m, 3H), 1.94-1.73 (m, 6H); MS (ESI) m/z 484 (M+H)+.
    • Example 460 4-((3-(Dimethylamino)propyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00497
  • 1H NMR (400 MHz, DMSO-d6) δ 11.13 (s, 1H), 8.87 (s, 1H), 8.38 (d, J=8.6 Hz, 1H), 7.84 (s, 1H), 7.69 (d, J=8.7 Hz, 2H), 7.38 (d, J=8.7 Hz, 1H), 7.23 (t, J=7.8 Hz, 2H), 6.97 (d, J=7.7 Hz, 2H), 6.82 (t, J=7.4 Hz, 1H), 6.66 (d, J=8.8 Hz, 2H), 6.46 (t, J=8.4 Hz, 1H), 4.29 (s, 2H), 3.11 (q, J=6.5 Hz, 2H), 2.29 (t, J=6.9 Hz, 2H), 2.14 (s, 6H), 1.68 (quint, J=6.9 Hz, 2H); [M+H]+: 444.
    • Example 461 4-((3-Morpholinopropyl)amino)-N-(3-oxo-7-(phenylamino) isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00498
  • 1H NMR (400 MHz, DMSO-d6) δ 11.13 (s, 1H), 8.87 (s, 1H), 8.38 (d, J=8.7 Hz, 1H), 7.85 (s, 1H), 7.69 (d, J=8.8 Hz, 2H), 7.38 (d, J=8.8 Hz, 1H), 7.23 (t, J=7.8 Hz, 2H), 6.97 (d, J=7.8 Hz, 2H), 6.82 (t, J=7.3 Hz, 1H), 6.66 (d, J=8.8 Hz, 3H), 6.48 (t, J=8.4 Hz, 1H), 4.29 (s, 2H), 3.59-3.55 (m, 5H), 3.13 (q, J=6.4 Hz, 2H), 2.38-2.31 (m, 5H), 1.73 (quint, J=6.9 Hz, 2H); [M+H]+: 486.
    • Example 462 N-(3-oxo-7-(phenylamino)isoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00499
  • 1H NMR (400 MHz, DMSO-d6) δ 11.13 (s, 1H), 8.87 (s, 1H), 8.38 (d, J=8.9 Hz, 1H), 7.85 (s, 1H), 7.69 (d, J=8.7 Hz, 2H), 7.38 (d, J=8.8 Hz, 1H), 7.23 (t, J=7.9 Hz, 2H), 6.97 (d, J=8.4 Hz, 2H), 6.82 (t, J=7.4 Hz, 1H), 6.66 (d, J=8.6 Hz, 3H), 6.49 (t, J=8.4 Hz, 1H), 4.29 (s, 2H), 3.14-3.09 (m, 3H), 2.42-2.38 (m, 6H), 1.68-1.66 (m, 7H); [M+H]+: 486.
    • Example 463 4-((3-(4-Methylpiperazin-1-yl)propyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00500
  • 1H NMR (400 MHz, DMSO-d6) δ 11.13 (s, 1H), 8.87 (s, 1H), 8.38 (d, J=8.6 Hz, 1H), 7.85 (s, 1H), 7.69 (d, J=8.2 Hz, 2H), 7.38 (d, J=8.7 Hz, 1H), 7.23 (t, J=7.5 Hz, 2H), 6.97 (d, J=7.8 Hz, 2H), 6.82 (t, J=7.2 Hz, 1H), 6.66 (d, J=8.7 Hz, 2H), 6.48 (t, J=8.4 Hz, 1H), 4.29 (s, 2H), 3.12-3.11 (m, 3H), 2.36-2.32 (m, 5H), 2.15-2.14 (m, 6H), 1.71-1.68 (m, 3H); [M+H]+: 499.
    • Example 464 4-((3-Hydroxypropyl)amino)-N-(3-oxo-7-(phenylamino) isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00501
  • 1H NMR (400 MHz, DMSO-d6) δ 11.13 (s, 1H), 8.87 (s, 1H), 8.38 (d, J=8.7 Hz, 1H), 7.84 (s, 1H), 7.69 (d, J=8.7 Hz, 2H), 7.38 (d, J=8.7 Hz, 1H), 7.23 (t, J=7.9 Hz, 2H), 6.97 (d, J=7.7 Hz, 2H), 6.82 (t, J=7.3 Hz, 1H), 6.66 (d, J=8.8 Hz, 1H), 6.43 (t, J=5.0 Hz, 1H), 4.52 (t, J=5.0 Hz, 1H), 4.29 (s, 2H), 3.51 (q, J=6.0 Hz, 2H), 3.15 (q, J=6.7 Hz, 2H), 1.71 (quint, J=6.6 Hz, 2H); [M+H]+: 417.
    • Example 465 N-(7-((3,5-bis(trifluoromethyl)phenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00502
  • 1H NMR (400 MHz, DMSO-d6) δ 11.21 (s, 1H), 8.96 (s, 1H), 8.71 (s, 1H), 8.48 (d, J=8.6 Hz, 1H), 7.71 (d, J=8.8 Hz, 2H), 7.52 (d, J=8.7 Hz, 1H), 7.35 (d, J=7.3 Hz, 3H), 6.70 (d, J=8.7 Hz, 2H), 6.41 (t, J=5.3 Hz, 1H), 4.31 (s, 2H), 3.22 (q, J=6.3 Hz, 2H), 2.62 (t, J=6.7 Hz, 2H), 1.69 (br s, 4H); [M+H]+ 592.
    • Example 466 N-(7-((3,5-bis(trifluoromethyl)phenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00503
  • 1H NMR (400 MHz, DMSO-d6) δ 11.21 (s, 1H), 8.96 (s, 1H), 8.71 (s, 1H), 8.49 (d, J=7.3 Hz, 1H), 7.71 (d, J=7.3 Hz, 2H), 7.53 (d, J=8.2 Hz, 1H), 7.35 (d, J=8.9 Hz, 3H), 6.66 (d, J=8.7 Hz, 2H), 6.54 (br s, 1H), 4.31 (s, 2H), 3.13 (q, J=6.3 Hz, 2H), 2.43 (m, 8H), 1.69 (br s, 4H); [M+H]+: 606.
    • Example 467 N-(7-((3,5-bis(trifluoromethyl)phenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00504
  • 1H NMR (400 MHz, DMSO-d6) δ 11.21 (s, 1H), 8.96 (s, 1H), 8.71 (s, 1H), 8.48 (d, J=8.7 Hz, 1H), 7.71 (d, J=8.8 Hz, 2H), 7.53 (d, J=8.8 Hz, 1H), 7.35 (d, J=7.2 Hz, 3H), 6.70 (d, J=8.9 Hz, 2H), 6.33 (t, J=5.3 Hz, 1H), 4.31 (s, 2H), 3.20 (q, J=6.1 Hz, 2H), 2.47-2.45 (m, 2H), 2.39 (br s, 4H), 1.51 (quint, J=5.5 Hz, 4H), 1.40-1.38 (m, 2H); [M+H]+: 606.
    • Example 468 N-(7-((3,5-bis(trifluoromethyl)phenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00505
  • 1H NMR (400 MHz, DMSO-d6) δ 11.21 (s, 1H), 8.96 (s, 1H), 8.70 (s, 1H), 8.48 (d, J=8.7 Hz, 1H), 7.70 (d, J=8.8 Hz, 2H), 7.52 (d, J=8.7 Hz, 1H), 7.35 (d, J=8.0 Hz, 3H), 6.66 (d, J=8.8 Hz, 2H), 6.56 (t, J=5.2 Hz, 1H), 4.31 (s, 2H), 3.12 (q, J=6.6 Hz, 2H), 2.32 (t, J=6.8 Hz, 5H), 1.69 (quint, J=7.0 Hz, 2H), 1.53-1.45 (m, 5H), 1.38-1.35 (m, 2H); [M+H]+: 620.
    • Example 469 N-(7-((2,3-dimethylphenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00506
  • 1H NMR (400 MHz, DMSO-d6) δ 11.09 (s, 1H), 8.82 (s, 1H), 8.29 (d, J=8.6 Hz, 1H), 7.67 (d, J=8.7 Hz, 2H), 7.23 (s, 1H), 7.01 (d, J=7.7 Hz, 1H), 6.87 (d, J=7.8 Hz, 1H), 6.79 (d, J=8.7 Hz, 2H), 6.73-6.67 (m, 3H), 6.33 (t, J=5.2 Hz, 1H), 4.19 (s, 2H), 3.21 (q, J=6.6 Hz, 4H), 2.61 (t, J=6.6 Hz, 2H), 2.26 (s, 3H), 2.08 (s, 3H), 1.69 (br s, 4H); [M+H]+: 484.
    • Example 470 N-(7-((2,3-dimethylphenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00507
  • 1H NMR (400 MHz, DMSO-d6) δ 11.08 (s, 1H), 8.82 (s, 1H), 8.29 (d, J=8.7 Hz, 1H), 7.67 (d, J=8.7 Hz, 2H), 7.23 (s, 1H), 7.01 (d, J=7.7 Hz, 1H), 6.87 (d, J=7.6 Hz, 1H), 6.79 (d, J=8.7 Hz, 2H), 6.69-6.63 (m, 3H), 6.46 (t, J=5.8 Hz, 1H), 4.19 (s, 2H), 3.12 (q, J=6.7 Hz, 2H), 2.47-2.42 (m, 6H), 2.26 (s, 3H), 2.08 (s, 3H), 1.74-1.68 (m, 6H); [M+H]+: 498.
    • Example 471 N-(7-((2,3-dimethylphenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00508
  • 1H NMR (400 MHz, DMSO-d6) δ 11.08 (s, 1H), 8.82 (s, 1H), 8.29 (d, J=8.8 Hz, 1H), 7.67 (d, J=8.8 Hz, 2H), 7.23 (s, 1H), 7.01 (d, J=7.9 Hz, 1H), 6.85 (d, J=5.6 Hz, 1H), 6.79 (d, J=8.8 Hz, 2H), 6.72-6.67 (m, 3H), 6.25 (t, J=5.4 Hz, 1H), 4.19 (s, 2H), 3.19 (q, J=6.6 Hz, 2H), 2.47-2.43 (m, 2H), 2.38 (br s, 4H), 2.26 (s, 3H), 2.08 (s, 3H), 1.52-1.48 (m, 4H), 1.38 (br s, 2H); [M+H]+: 498.
    • Example 472 N-(7-((2,3-dimethylphenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00509
  • 1H NMR (400 MHz, DMSO-d6) δ 11.08 (s, 1H), 8.82 (s, 1H), 8.29 (d, J=8.8 Hz, 1H), 7.67 (d, J=8.7 Hz, 2H), 7.23 (s, 1H), 7.01 (d, J=7.7 Hz, 1H), 6.86 (d, J=7.5 Hz, 1H), 6.79 (d, J=8.8 Hz, 2H), 6.69-6.63 (m, 3H), 6.49 (t, J=5.0 Hz, 1H), 4.19 (s, 2H), 3.11 (q, J=6.4 Hz, 2H), 2.32-2.28 (m, 5H), 2.26 (s, 3H), 2.08 (s, 3H), 1.69 (t, J=6.8 Hz, 2H), 1.51-1.49 (m, 5H), 1.38 (br s, 2H); [M+H]+ 512.
    • Example 473 N-(3-oxo-7-(o-tolylamino)isoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00510
  • 1H NMR (400 MHz, DMSO-d6) δ 11.12 (s, 1H), 8.83 (s, 1H), 8.34 (d, J=8.6 Hz, 1H), 7.69 (d, J=8.8 Hz, 2H), 7.21-7.18 (m, 2H), 7.09 (t, J=7.4 Hz, 1H), 6.97 (d, J=8.7 Hz, 1H), 6.87 (t, J=7.4 Hz, 2H), 6.69 (d, J=8.8 Hz, 2H), 6.34 (t, J=5.4 Hz, 1H), 4.18 (s, 2H), 3.21 (q, J=6.5 Hz, 2H), 2.62 (t, J=6.7 Hz, 2H), 2.20 (s, 3H), 1.69-1.68 (m, 8H); [M+H]+: 470.
    • Example 474 N-(7-((2-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00511
  • 1H NMR (400 MHz, DMSO-d6) δ 11.14 (s, 1H), 8.84 (s, 1H), 8.35 (d, J=9.0 Hz, 1H), 7.17 (d, J=8.7 Hz, 1H), 7.12 (s, 1H), 7.00 (d, J=7.4 Hz, 1H), 6.88-6.82 (m, 3H), 6.69 (d, J=8.8 Hz, 2H), 6.35 (t, J=7.4 Hz, 1H), 4.28 (s, 2H), 3.82 (s, 3H), 3.21 (q, J=6.3 Hz, 2H), 2.62 (t, J=6.3 Hz, 3H), 1.70 (br s, 7H); [M+H]+: 486.
    • Example 475 N-(7-((2-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00512
  • 1H NMR (400 MHz, DMSO-d6) δ 11.14 (s, 1H), 8.84 (s, 1H), 8.35 (d, J=8.7 Hz, 1H), 7.69 (d, J=8.7 Hz, 3H), 7.17 (d, J=8.7 Hz, 1H), 7.12 (s, 1H), 7.00 (d, J=7.8 Hz, 1H), 6.88-6.82 (m, 3H), 6.65 (d, J=8.8 Hz, 3H), 6.48 (t, J=5.1 Hz, 1H), 4.28 (s, 2H), 3.82 (s, 3H), 3.13 (q, J=6.7 Hz, 2H), 2.47-2.45 (m, 2H), 2.42 (br s, 4H), 1.47-1.70 (m, 2H), 1.68-1.67 (m, 4H); [M+H]+ 500.
    • Example 476 N-(3-oxo-7-(o-tolylamino)isoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00513
  • 1H NMR (400 MHz, DMSO-d6) δ 11.12 (s, 1H), 8.83 (s, 1H), 8.34 (d, J=8.7 Hz, 1H), 7.68 (d, J=8.9 Hz, 3H), 7.19 (d, J=5.6 Hz, 2H), 7.09 (d, J=8.1 Hz, 1H), 6.97 (d, J=8.6 Hz, 1H), 6.91-6.85 (m, 2H), 6.65 (d, J=8.9 Hz, 4H), 6.47 (t, J=5.5 Hz, 1H), 4.18 (s, 2H), 3.13 (q, J=5.5 Hz, 2H), 2.47-2.42 (m, 2H), 2.38 (br s, 5H), 2.20 (s, 3H), 1.68-1.67 (m, 5H); [M+H]+: 484.
    • Example 477 N-(7-((2-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00514
  • 1H NMR (400 MHz, DMSO-d6) δ 11.14 (s, 1H), 8.84 (s, 1H), 8.35 (d, J=8.8 Hz, 1H), 7.69 (d, J=8.8 Hz, 2H), 7.17 (d, J=8.8 Hz, 1H), 7.12 (s, 1H), 7.00 (d, J=7.8 Hz, 1H), 6.88-6.82 (m, 3H), 6.69 (d, J=8.8 Hz, 2H), 6.27 (t, J=5.3 Hz, 1H), 4.28 (s, 2H), 3.82 (s, 3H), 3.20 (q, J=6.3 Hz, 2H), 2.47-2.45 (m, 2H), 2.33 (br s, 4H), 1.50 (q, J=5.4 Hz, 4H), 1.38 (br s, 2H); [M+H]+ 500.
    • Example 478 N-(7-((2-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00515
  • 1H NMR (400 MHz, DMSO-d6) δ 11.14 (s, 1H), 8.84 (s, 1H), 8.35 (d, J=8.8 Hz, 1H), 7.69 (d, J=8.8 Hz, 2H), 7.17 (d, J=8.8 Hz, 1H), 7.12 (s, 1H), 7.00 (d, J=7.8 Hz, 1H), 6.88-6.82 (m, 3H), 6.65 (d, J=8.8 Hz, 2H), 6.51 (t, J=5.5 Hz, 1H), 4.28 (s, 2H), 3.82 (s, 3H), 3.11 (q, J=6.4 Hz, 2H), 2.34-2.31 (m, 5H), 1.69 (quint, J=6.9 Hz, 2H), 1.51-1.49 (m, 5H), 1.38 (br s, 2H); [M+H]+ 514.
    • Example 479 N-(3-oxo-7-(phenylamino)isoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00516
  • 1H NMR (400 MHz, DMSO-d6) δ 11.13 (s, 1H), 8.88 (s, 1H), 8.38 (d, J=8.7 Hz, 1H), 7.84 (s, 1H), 7.69 (d, J=8.8 Hz, 2H), 7.38 (d, J=8.8 Hz, 1H), 7.23 (d, J=7.9 Hz, 2H), 6.97 (d, J=7.7 Hz, 2H), 6.82 (t, J=7.3 Hz, 1H), 6.66 (d, J=8.8 Hz, 2H), 6.51 (t, J=5.4 Hz, 1H), 4.29 (s, 2H), 3.11 (q, J=6.5 Hz, 2H), 2.34-2.31 (m, 5H), 1.69 (quint, J=6.9 Hz, 2H), 1.53-1.47 (m, 5H), 1.39-1.38 (m, 2H); [M+H]+: 484.
    • Example 480 N-(3-oxo-7-(phenylamino)isoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide hydrochloride
  • Figure US20160311772A1-20161027-C00517
  • 1H NMR (400 MHz, DMSO-d6) δ 11.15 (s, 1H), 9.21 (br s, 1H), 8.67 (s, 1H), 8.37 (d, J=8.6 Hz, 1H), 7.86 (s, 1H), 7.72 (d, J=8.6 Hz, 2H), 7.37 (d, J=3.3 Hz, 1H), 7.23 (t, J=8.0 Hz, 2H), 6.97 (d, J=8.0 Hz, 2H), 6.82 (t, J=7.3 Hz, 1H), 6.70 (d, J=8.9 Hz, 2H), 6.55 (br s, 1H), 4.29 (s, 2H), 3.44-3.37 (m, 2H), 3.20-3.18 (m, 2H), 3311-3.90 (m, 2H), 2.86 (q, J=11.5 Hz, 2H), 1.95-1.90 (m, 2H), 1.82-1.79 (m, 2H), 1.70-1.63 (m, 3H); [M+H]+: 484.
    • Example 481 4-((2-Aminoethyl)amino)-N-(3-oxo-7-(phenylamino) isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00518
  • 1H NMR (400 MHz, DMSO-d6) δ 11.13 (s, 1H), 8.87 (s, 1H), 8.38 (d, J=8.4 Hz, 1H), 7.84 (s, 1H), 7.69 (d, J=8.5 Hz, 2H), 7.38 (d, J=8.7 Hz, 1H), 7.23 (d, J=8.1 Hz, 2H), 6.97 (d, J=7.6 Hz, 2H), 6.82 (t, J=7.5 Hz, 1H), 6.68 (d, J=8.3 Hz, 2H), 6.43 (t, J=5.8 Hz, 1H), 4.29 (s, 2H), 3.09 (q, J=5.1 Hz, 2H), 2.73 (t, J=6.3 Hz, 2H); [M+H]+: 402.
    • Example 482 N-(3-oxo-7-(o-tolylamino)isoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00519
  • 1H NMR (400 MHz, DMSO-d6) δ 11.12 (s, 1H), 8.82 (s, 1H), 8.34 (d, J=8.6 Hz, 1H), 7.68 (d, J=8.8 Hz, 2H), 7.19 (d, J=7.0 Hz, 2H), 7.09 (t, J=7.3 Hz, 1H), 6.97 (d, J=8.8 Hz, 2H), 6.91-6.85 (m, 2H), 6.68 (d, J=8.8 Hz, 3H), 6.25 (t, J=5.3 Hz, 1H), 4.18 (s, 2H), 3.19 (q, J=6.4 Hz, 2H), 2.45-2.35 (m, 5H), 2.32 (s, 3H), 1.52-1.48 (m, 5H), 1.38 (br s, 2H); [M+H]+: 484.
    • Example 483 N-(3-oxo-7-(o-tolylamino)isoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide
  • Figure US20160311772A1-20161027-C00520
  • 1H NMR (400 MHz, DMSO-d6) δ 11.12 (s, 1H), 8.82 (s, 1H), 8.34 (d, J=8.8 Hz, 1H), 7.68 (d, J=8.8 Hz, 2H), 7.18 (d, J=7.3 Hz, 2H), 7.09 (t, J=7.4 Hz, 1H), 6.97 (d, J=8.7 Hz, 1H), 6.91-6.87 (m, 2H), 6.65 (d, J=8.9 Hz, 4H), 6.50 (t, J=5.3 Hz, 1H), 4.18 (s, 2H), 3.11 (q, J=6.2 Hz, 2H), 2.32-2.31 (m, 5H), 2.22 (s, 3H), 1.71-1.68 (2, 5H), 1.53-1.46 (m, 5H), 1.38 (br s, 2H); [M+H]+: 498.
    • Example 484 4-((4-Hydroxybutyl)amino)-N-(3-oxo-7-(phenylamino) isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00521
  • 1H NMR (400 MHz, DMSO-d6) δ 11.12 (s, 1H), 8.86 (s, 1H), 8.38 (d, J=8.7 Hz, 1H), 7.84 (s, 1H), 7.69 (d, J=8.7 Hz, 3H), 7.44 (d, J=7.0 Hz, 1H), 7.22 (t, J=7.9 Hz, 3H), 6.97 (d, J=7.7 Hz, 2H), 6.83-6.79 (m, 1H), 6.66 (d, J=8.8 Hz, 3H), 6.47-6.43 (m, 1H), 4.43 (t, J=5.1 Hz, 1H), 4.29 (s, 2H), 3.43 (q, J=6.1 Hz, 2H), 3.09 (q, J=6.2 Hz, 2H), 1.61-1.50 (m, 4H); [M+H]+: 431.
    • Example 485 4-((2-Acetamidoethyl)amino)-N-(3-oxo-7-(phenylamino) isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00522
  • 1H NMR (400 MHz, DMSO-d6) δ 11.14 (s, 1H), 8.87 (s, 1H), 8.38 (d, J=8.7 Hz, 1H), 7.84 (s, 1H), 7.70 (d, J=8.8 Hz, 2H), 7.38 (d, J=8.8 Hz, 1H), 7.23 (t, J=7.9 Hz, 2H), 6.97 (d, J=7.6 Hz, 2H), 6.82 (t, J=7.3 Hz, 1H), 6.69 (d, J=8.9 Hz, 2H), 6.49 (t, J=5.2 Hz, 1H), 4.29 (s, 2H), 3.22-3.16 (m, 4H), 1.82 (s, 3H); [M+H]+: 444.
    • Example 486 4-((3-Aminopropyl)amino)-N-(3-oxo-7-(phenylamino) isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00523
  • 1H NMR (400 MHz, DMSO-d6) δ 11.13 (s, 1H), 8.87 (s, 1H), 8.38 (d, J=8.7 Hz, 1H), 7.84 (s, 1H), 7.69 (d, J=8.9 Hz, 3H), 7.38 (d, J=8.7 Hz, 1H), 7.23 (t, J=7.8 Hz, 3H), 6.97 (d, J=7.7 Hz, 2H), 6.82 (t, J=7.2 Hz, 1H), 6.66 (d, J=8.9 Hz, 4H), 4.29 (s, 2H), 3.42-3.33 (m, 2H), 3.29-3.26 (m, 2H), 3.15-3.13 (m, 2H); [M+H]+: 416.
    • Example 487 4-((2-Hydroxyethyl)amino)-N-(3-oxo-7-(phenylamino) isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00524
  • 1H NMR (400 MHz, DMSO-d6) δ 11.12 (s, 1H), 8.85 (s, 1H), 8.37 (d, J=8.5 Hz, 1H), 7.83 (s, 1H), 7.69 (d, J=8.4 Hz, 2H), 7.38 (d, J=8.8 Hz, 1H), 7.23 (t, J=7.9 Hz, 2H), 6.97 (d, J=7.8 Hz, 2H), 6.82 (t, J=7.2 Hz, 1H), 6.69 (d, J=8.8 Hz, 2H), 6.39 (d, J=5.9 Hz, 1H), 4.76 (t, J=5.5 Hz, 1H), 4.29 (s, 2H), 3.57 (q, J=5.6 Hz, 2H), 3.18 (q, J=5.32 Hz, 2H); [M+H]+: 403.
    • Example 488 4-((2-Hydroxy-3-(piperidin-1-yl)propyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00525
  • 1H NMR (400 MHz, DMSO-d6) δ 11.13 (s, 1H), 8.86 (s, 1H), 8.38 (d, J=8.8 Hz, 1H), 7.83 (s, 1H), 7.68 (d, J=8.8 Hz, 2H), 7.38 (d, J=8.4 Hz, 1H), 7.23 (t, J=8.0 Hz, 2H), 6.97 (d, J=7.6 Hz, 2H), 6.82 (t, J=7.2 Hz, 1H), 6.71 (d, J=8.8 Hz, 2H), 6.44 (t, J=5.6 Hz, 1H), 4.68 (d, J=4.8 Hz, 1H), 4.29 (s, 2H), 3.79-3.76 (m, 1H), 3.26-3.20 (m, 1H), 3.06-3.00 (m, 1H), 2.39-2.28 (m, 6H), 1.52-1.48 (m, 4H), 1.39-1.37 (m, 2H). [M+H]+ 500.
    • Example 489 (S)-4-((2-hydroxy-3-(piperidin-1-yl)propyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00526
  • 1H NMR (400 MHz, DMSO-d6) δ 11.13 (s, 1H), 8.86 (s, 1H), 8.38 (d, J=8.8 Hz, 1H), 7.83 (s, 1H), 7.68 (d, J=8.8 Hz, 2H), 7.38 (d, J=8.4 Hz, 1H), 7.23 (t, J=8.0 Hz, 2H), 6.97 (d, J=7.6 Hz, 2H), 6.82 (t, J=7.2 Hz, 1H), 6.71 (d, J=8.8 Hz, 2H), 6.44 (t, J=5.6 Hz, 1H), 4.68 (d, J=4.8 Hz, 1H), 4.29 (s, 2H), 3.79-3.76 (m, 1H), 3.26-3.20 (m, 1H), 3.06-3.00 (m, 1H), 2.39-2.28 (m, 6H), 1.52-1.48 (m, 4H), 1.39-1.37 (m, 2H). [M+H]+ 500.
    • Example 490 (R)-4-((2-hydroxy-3-(piperidin-1-yl)propyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00527
  • 1H NMR (400 MHz, DMSO-d6) δ 11.13 (s, 1H), 8.86 (s, 1H), 8.38 (d, J=8.8 Hz, 1H), 7.83 (s, 1H), 7.68 (d, J=8.8 Hz, 2H), 7.38 (d, J=8.4 Hz, 1H), 7.23 (t, J=8.0 Hz, 2H), 6.97 (d, J=7.6 Hz, 2H), 6.82 (t, J=7.2 Hz, 1H), 6.71 (d, J=8.8 Hz, 2H), 6.44 (t, J=5.6 Hz, 1H), 4.68 (d, J=4.8 Hz, 1H), 4.29 (s, 2H), 3.79-3.76 (m, 1H), 3.26-3.20 (m, 1H), 3.06-3.00 (m, 1H), 2.39-2.28 (m, 6H), 1.52-1.48 (m, 4H), 1.39-1.37 (m, 2H). [M+H]+ 500.
    • Example 491 4-(4-Aminopiperidin-1-yl)-N-(3-oxo-7-(phenylamino) isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00528
  • 1H NMR (400 MHz, DMSO-d6) δ 11.19 (s, 1H), 8.88 (s, 1H), 8.38 (d, J=8.8 Hz, 1H), 7.86 (s, 1H), 7.77 (d, J=9.2 Hz, 2H), 7.38 (d, J=8.8 Hz, 1H), 7.23 (t, J=8.0 Hz, 2H), 7.04 (d, J=9.2 Hz, 2H), 6.98 (d, J=7.6 Hz, 2H), 6.82 (t, J=7.4 Hz, 1H), 4.29 (s, 2H), 3.84 (d, J=13.2 Hz, 2H), 2.92-2.86 (m, 2H), 2.81-2.76 (m, 1H), 1.79-1.74 (m, 2H), 1.31-1.23 (m, 2H). [M+H]+: 442.
    • Example 492 4-((2-(Azepan-1-yl)ethyl)amino)-N-(3-oxo-7-(phenylamino) isoindolin-4-yl)benzamide
  • Figure US20160311772A1-20161027-C00529
  • 1H NMR (400 MHz, DMSO-d6) δ 11.13 (s, 1H), 8.87 (s, 1H), 8.37 (d, J=8.8 Hz, 1H), 7.85 (s, 1H), 7.69 (d, J=8.4 Hz, 2H), 7.38 (d, J=8.8 Hz, 1H), 7.23 (t, J=7.8 Hz, 2H), 6.97 (d, J=7.6 Hz, 2H), 6.82 (d, J=7.4 Hz, 1H), 6.69 (d, J=8.8 Hz, 2H), 6.23 (t, J=5.6 Hz, 1H), 4.29 (s, 2H), 3.17 (q, J=6.4 Hz, 2H), 2.68-2.64 (m, 6H), 1.58-1.55 (m, 8H). [M+H]+: 484.
    • Experimental Example Inhibition Activities on TNIK, IKKε and TBK1
  • Inhibition activities on TNIK, IKKε and TBK1 were evaluated using the compounds of Examples 1 to 492.
  • The inhibition activities on TNIK, IKKε and TBK1 were measured by a luminometer, TNIK/IKKε/TBK1 Kinase Enzyme System (Promega, Ca# V4158; Invitrogen, PR8031B, Promega, Ca# V3991) and ADP-Glo Kinase Assay using ADP-Glo™ Kinase Analysis Kit (Promega, Ca# V9101) and a kinase reaction buffer [40 mM Tris(pH 7.5), 20 mM MgCl2, 0.1 mg/mL BSA] in accordance with the manufacturer's protocol.
  • The results of the inhibition activities of the compounds of Examples 1 to 492 against TNIK, IKKε and TBK1 are shown in Table 1 below.
  • TABLE 1
    TNIK TBK1 IKKε
    Example Name (μM) (μM) (μM)
    1 N-(7-(2-ethylphenyl)-3-oxoisoindolin-4-yl)benzamide 3.1
    2 N-(7-(3-isopropylphenyl)-3-oxoisoindolin-4-yl)benzamide >20
    3 N-(7-(4-(tert-butyl)phenyl)-3-oxoisoindolin-4-yl)benzamide >20
    4 N-(3-oxo-7-(2-(trifluoromethoxy)phenyl)isoindolin-4-yl)benzamide 3
    5 N-(3-oxo-7-(3-(trifluoromethoxy)phenyl)isoindolin-4-yl)benzamide >20
    6 N-(7-(2-isopropoxyphenyl)-3-oxoisoindolin-4-yl)benzamide >20
    7 N-(7-(3-isopropoxyphenyl)-3-oxoisoindolin-4-yl)benzamide >20
    8 methyl 2-(7-benzamido-1-oxoisoindolin-4-yl)benzo ate >20
    9 methyl 3-(7-benzamido-1-oxoisoindolin-4-yl)benzo ate >20
    10 methyl 4-(7-benzamido-1-oxoisoindolin-4-yl)benzo ate Insoluble
    11 N-(7-(2-acetylphenyl)-3-oxoisoindolin-4-yl)benzamide 9.5
    12 N-(7-(3-acetylphenyl)-3-oxoisoindolin-4-yl)benzamide >20
    13 N-(7-(4-acetylphenyl)-3-oxoisoindolin-4-yl)benzamide Insoluble
    14 N-(7-(2-(methylthio)phenyl)-3-oxoisoindolin-4-yl)benzamide 1.1
    15 N-(7-(2,4-difluorophenyl)-3-oxoisoindolin-4-yl)benzamide >20
    16 N-(7-(2,3-dimethylphenyl)-3-oxoisoindolin-4-yl)benzamide 1.3
    17 N-(7-(2,3-dichlorophenyl)-3-oxoisoindolin-4-yl)benzamide 1
    18 N-(7-(2,4-dichlorophenyl)-3-oxoisoindolin-4-yl)benzamide >20
    19 N-(7-(2,5-dichlorophenyl)-3-oxoisoindolin-4-yl)benzamide Insoluble
    20 N-(7-(3,4-dichlorophenyl)-3-oxoisoindolin-4-yl)benzamide >20
    21 N-(7-(3,5-dichlorophenyl)-3-oxoisoindolin-4-yl)benzamide >20
    22 N-(7-(4-fluoro-2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide Insoluble
    23 N-(7-(2-chloro-3-fluorophenyl)-3-oxoisoindolin-4-yl)benzamide 8.9
    24 N-(7-(2-fluoro-3-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide >20
    25 N-(3-oxo-7-(2,3,4-trimethoxyphenyl)isoindolin-4-yl)benzamide Insoluble
    26 N-(7-(3,4-dimethylphenyl)-3-oxoisoindolin-4-yl)benzamide 3.8
    27 N-(7-(3,5-dimethylphenyl)-3-oxoisoindolin-4-yl)benzamide 3
    28 N-(7-(2,6-dimethylphenyl)-3-oxoisoindolin-4-yl)benzamide 1.7
    29 N-(7-ethyl-3-oxoisoindolin-4-yl)benzamide 1.8
    30 N-(7-(3,5-difluorophenyl)-3-oxoisoindolin-4-yl)benzamide >20
    31 N-(7-(2,5-dimethylphenyl)-3-oxoisoindolin-4-yl)benzamide 1.6
    32 N-(7-(2,5-difluorophenyl)-3-oxoisoindolin-4-yl)benzamide 1
    33 N-(7-(3,4-difluorophenyl)-3-oxoisoindolin-4-yl)benzamide 3.7
    34 N-(7-(2,3-difluorophenyl)-3-oxoisoindolin-4-yl)benzamide 0.54
    35 N-(7-butyl-3-oxoisoindolin-4-yl)benzamide 8.6
    36 4-fluoro-N-(3-oxo-7-propylisoindolin-4-yl)benzamide >20
    37 N-(7-methyl-3-oxoisoindolin-4-yl)benzamide 6.1
    38 N-(7-(2,4-dimethylphenyl)-3-oxoisoindolin-4-yl)benzamide 1.7
    39 N-(7-(4-ethylphenyl)-3-oxoisoindolin-4-yl)benzamide 6.1
    40 N-(7-(4-isopropoxyphenyl)-3-oxoisoindolin-4-yl)benzamide >20
    41 N-(7-(4-(methylthio)phenyl)-3-oxoisoindolin-4-yl)benzamide 1.2
    42 N-(7-(3-ethylphenyl)-3-oxoisoindolin-4-yl)benzamide 3.7
    43 N-(3-oxo-7-(2-propoxyphenyl)isoindolin-4-yl)benzamide >20
    44 N-(3-oxo-7-(3-propoxyphenyl)isoindolin-4-yl)benzamide >20
    45 N-(7-(2-butoxyphenyl)-3-oxoisoindolin-4-yl)benzamide >20
    46 N-(7-(3-butoxyphenyl)-3-oxoisoindolin-4-yl)benzamide >20
    47 N-(7-(2-(methylsulfonyl)phenyl)-3-oxoisoindolin-4-yl)benzamide >20
    48 N-(7-(3-fluoro-2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide 0.49
    49 N-(7-(4-chloro-2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide >20
    50 N-(7-(3-chloro-2-fluorophenyl)-3-oxoisoindolin-4-yl)benzamide >20
    51 N-(3-oxo-7-(thiazol-5-yl)isoindolin-4-yl)benzamide 0.44
    52 N-(3-oxo-7-(thiazol-4-yl)isoindolin-4-yl)benzamide 2.80
    53 N-(3-oxo-7-(thiazol-2-yl)isoindolin-4-yl)benzamide 2.34
    54 N-(7-(1H-imidazol-4-yl)-3-oxoisoindolin-4-yl)benzamide 3.82
    55 N-(3-oxo-7-(1H-pyrazol-4-yl)isoindolin-4-yl)benzamide 4.62
    56 N-(7-(1-methyl-1H-imidazol-5-yl)-3-oxoisoindolin-4-yl)benzamide 2.21
    57 N-(7-(1-methyl-1H-pyrazol-4-yl)-3-oxoisoindolin-4-yl)benzamide 2.17
    58 N-(3-oxo-7-(1H-1,2,4-triazol-5-yl)isoindolin-4-yl)benzamide 2.67
    59 N-(7-(1-methyl-1H-1,2,4-triazol-5-yl)-3-oxoisoindolin-4-yl)benzamide >20
    60 7-amino-4-(4-methoxyphenyl)isoindolin-1-one >20
    61 7-amino-4-(4-fluorophenyl)isoindolin-1-one Insoluble
    62 7-amino-4-(4-chlorophenyl)isoindolin-1-one >20
    63 7-amino-4-(p-tolyl)isoindolin-1-one >20
    64 4-(4-acetylphenyl)-7-aminoisoindolin-1-one >20
    65 7-amino-4-(pyridin-4-yl)isoindolin-1-one >20
    66 7-amino-4-(2,6-dichloropyrimidin-4-yl)isoindolin-1-one
    67 7-amino-4-(2-chloropyrimidin-4-yl)isoindolin-1-one
    68 7-amino-4-(2-((3-methoxyphenyl)amino)pyridin-4-yl)isoindolin-1-one 1.24 2.64
    69 7-amino-4-(4-((3-methoxyphenyl)amino)pyridin-2-yl)isoindolin-1-one >10
    70 7-amino-4-(2-((3-methoxyphenyl)amino)pyrimidin-4-yl)isoindolin-1-one 0.051 0.051
    71 7-amino-4-(2-((1-methyl-1H-p yrazol-4-yl)amino)pyrimidin-4-yl)isoindolin-1-one 0.15 0.16
    72 7-amino-4-(2-(phenylamino)pyrimidin-4-yl)isoindolin-1-one 0.09 0.28
    73 7-amino-4-(2-((3-fluorophenyl)amino)pyrimidin-4-yl)isoindolin-1-one 0.035 0.35
    74 7-amino-4-(2-((4-fluorophenyl)amino)pyrimidin-4-yl)isoindolin-1-one 0.043 0.56
    75 7-amino-4-(2-((4-methoxyphenyl)amino)pyrimidin-4-yl)isoindolin-1-one 0.11 0.36
    76 N-(4-((4-(7-amino-1-oxoisoindolin-4-yl)pyrimidin-2-yl)amino)phenyl)acetamide 0.1 0.35
    77 N-(3-((4-(7-amino-1-oxoisoindolin-4-yl)pyrimidin-2-yl)amino)phenyl)acetamide 0.027 0.2
    78 7-amino-4-(6-((3-methoxyphenyl)amino)pyrimidin-4-yl)isoindolin-1-one 0.19 1.39
    79 7-amino-4-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)isoindolin-1-one 0.64 10
    80 7-amino-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)isoindolin-1-one 9.23 >10
    81 7-amino-4-(2-(4-methylpiperazin-1-yl)pyrimidin-4-yl)isoindolin-1-one >10 >10
    82 7-amino-4-(2-morpholinopyrimidin-4-yl)isoindolin-1-one >10 >10
    83 7-amino-4-(2-(p-tolylamino)pyrimidin-4-yl)isoindolin-1-one 0.38 0.87
    84 7-amino-4-(2-(m-tolylamino)pyrimidin-4-yl)isoindolin-1-one 0.2 0.44
    85 N-(4-(3-(7-amino-1-oxoisoindolin-4-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)acetamide 0.072 0.16
    86 7-amino-4-(5-(5-(morpholinomethyl)thiophen-2-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)isoindolin-1-one 0.032 0.056
    87 2-methyl-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 14.6
    88 3-methyl-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 2.8
    89 4-methyl-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 0.77
    90 3-chloro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide >20
    91 2,4-difluoro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide >20
    92 3,4-difluoro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide >20
    93 3,4-dimethyl-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 1.1
    94 2-(dimethylamino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide >20
    95 3-(dimethylamino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide Insoluble
    96 2-(methylthio)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 7
    97 3-(methylthio)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide >20
    98 2-(methylsulfonyl)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 10.5
    99 3-(methylsulfonyl)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 4.3
    100 4-(methylsulfonyl)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide >20
    101 2,4-dimethoxy-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide >20
    102 3,4-dimethoxy-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide Insoluble
    103 2,4-dichloro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide >20
    104 3,4-dichloro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide Insoluble
    105 2,4-dimethyl-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide >20
    106 2-acetamido-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide >20
    107 3-acetamido-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 0.48
    108 4-(methylamino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 0.78
    109 3-methyl-N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide >20
    110 4-methyl-N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide >20
    111 5-methyl-N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide 0.54
    112 N-(3-oxo-7-(o-tolyl)isoindolin-4-yl)benzamide 2.2
    113 N-(3-oxo-7-(m-tolyl)isoindolin-4-yl)benzamide 1.7
    114 N-(3-oxo-7-(2-(trifluoromethyl)phenyl)isoindolin-4-yl)benzamide >20
    115 N-(3-oxo-7-(3-(trifluoromethyl)phenyl)isoindolin-4-yl)benzamide >20
    116 4-acetamido-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 0.13
    117 N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 2.32
    118 N-(7-(4-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide >20
    119 4-nitro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide Insoluble
    120 4-acetamido-N-(7-(4-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide >20
    121 4-methoxy-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 3.4
    122 4-fluoro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 2.2
    123 N-(7-(4-fluorophenyl)-3-oxoisoindolin-4-yl)-4-methoxybenzamide 7.0
    124 4-acetamido-N-(7-(4-fluorophenyl)-3-oxoisoindolin-4-yl)benzamide 0.17
    125 N-(3-oxo-7-(thiophen-2-yl)isoindolin-4-yl)benzamide 1.4
    126 N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)benzamide 0.6
    127 N-(3-oxo-7-(pyridin-4-yl)isoindolin-4-yl)benzamide Insoluble
    128 N-(3-oxo-7-(pyridin-4-yl)isoindolin-4-yl)benzamide hydrochloride >20
    129 2-methoxy-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide >20
    130 3-fluoro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide >20
    131 4-(methylthio)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 2.3
    132 N-(3-oxo-7-(4-propoxyphenyl)isoindolin-4-yl)benzamide >20
    133 N-(7-(4-isopropylphenyl)-3-oxoisoindolin-4-yl)benzamide >20
    134 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)furan-2-carboxamide 0.054
    135 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-fluorobenzamide 0.14
    136 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)thiophene-2-carboxamide 0.068
    137 4-fluoro-2-methyl-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide >20
    138 4-acetamido-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide 0.2
    139 4-(dimethylamino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 1.8
    140 4-acetamido-N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)benzamide 0.3
    141 4-fluoro-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide 1.6
    142 2-fluoro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 0.95
    143 4-chloro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 1.1
    144 N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide 0.7
    145 N-(7-(3-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide 1.3
    146 N-(3-oxo-7-(thiophen-3-yl)isoindolin-4-yl)benzamide >20
    147 N-(7-(3-cyanophenyl)-3-oxoisoindolin-4-yl)benzamide >20
    148 N-(7-(3-(dimethylamino)phenyl)-3-oxoisoindolin-4-yl)benzamide 7.4
    149 N-(7-(2-fluorophenyl)-3-oxoisoindolin-4-yl)benzamide 3.8
    150 N-(7-(furan-3-yl)-3-oxoisoindolin-4-yl)benzamide 2.7
    151 N-(7-(3-fluorophenyl)-3-oxoisoindolin-4-yl)benzamide 1.5
    152 N-(3-oxo-7-(pyridin-3-yl)isoindolin-4-yl)benzamide >20
    153 N-(3-oxo-7-(pyridin-3-yl)isoindolin-4-yl)benzamide hydrochloride
    154 N-(3-oxo-7-(pyrimidin-5-yl)isoindolin-4-yl)benzamide >20
    155 3-chloro-N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide 2.29
    156 5-bromo-N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide 2.86
    157 3-bromo-N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide 3.40
    158 4-fluoro-N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)benzamide 1.27
    159 N-(3-oxo-7-phenylisoindolin-4-yl)pentanamide 1.8
    160 N-(3-oxo-7-phenylisoindolin-4-yl)acetamide 1.1
    161 N-(7-(2-chloropyrimidin-4-yl)-3-oxoisoindolin-4-yl)acetamide
    162 N-(7-(2-((3-methoxyphenyl)amino)pyrimidin-4-yl)-3-oxoisoindolin-4-yl)acetamide 0.1 0.63
    163 N-(7-(2-((3-fluorophenyl)amino)pyrimidin-4-yl)-3-oxoisoindolin-4-yl)acetamide 4 >10
    164 N-(3-oxo-7-(2-(m-tolylamino)pyrimidin-4-yl)isoindolin-4-yl)acetamide 0.35 0.83
    165 N-(3-oxo-7-(2-(p-tolylamino)pyrimidin-4-yl)isoindolin-4-yl)acetamide >10 >10
    166 N-(7-(2-((3-methoxyphenyl)amino)pyrimidin-4-yl)-3-oxoisoindolin-4-yl)propionamide 0.094 >10
    167 N-(7-(4-(methylsulfonyl)phenyl)-3-oxoisoindolin-4-yl)benzamide 9.8
    168 N-(7-(3-(methylsulfonyl)phenyl)-3-oxoisoindolin-4-yl)benzamide >20
    169 N-(7-(3-acetamidophenyl)-3-oxoisoindolin-4-yl)benzamide 4.2
    170 5-chloro-N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide 3.52
    171 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide 0.057
    172 N-(7-(3,5-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide >20
    173 N-(7-cyclopropyl-3-oxoisoindolin-4-yl)benzamide 0.75
    174 N-(7-(2-chlorophenyl)-3-oxoisoindolin-4-yl)benzamide >20
    175 N-(7-(2,4-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide 3
    176 N-(7-(3,4-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide >20
    177 N-(7-(3-ethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide 8.1
    178 N-(7-(2,5-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide >20
    179 N-(7-(4-chlorophenyl)-3-oxoisoindolin-4-yl)benzamide >20
    180 N-(7-(3-chlorophenyl)-3-oxoisoindolin-4-yl)benzamide 13.7
    181 N-(7-(4-ethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide >20
    182 N-(7-(2-ethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide 2.8
    183 N-(7-(2-cyanophenyl)-3-oxoisoindolin-4-yl)benzamide 1.7
    184 N-(7-(4-butoxyphenyl)-3-oxoisoindolin-4-yl)benzamide >20
    185 N-(7-(2-(dimethylamino)phenyl)-3-oxoisoindolin-4-yl)benzamide 2.8
    186 N-(3-oxo-7-(4-(trifluoromethoxy)phenyl)isoindolin-4-yl)benzamide >20
    187 N-(7-(2,6-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide 2.2
    188 N-(3-oxo-7-(4-propylphenyl)isoindolin-4-yl)benzamide >20
    189 N-(7-(2,3-dihydroxyphenyl)-3-oxoisoindolin-4-yl)-4-fluorobenzamide Insoluble
    190 4-fluoro-N-(7-(2-hydroxy-3-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide 0.52
    191 4-fluoro-N-(3-oxo-7-(thiophen-2-yl)isoindolin-4-yl)benzamide 13.34
    192 5-methyl-N-(3-oxo-7-phenylisoindolin-4-yl)furan-2-carboxamide 0.73
    193 N-(7-(benzordloxazol-7-yl)-3-oxoisoindolin-4-yl)-4-fluorobenzamide 1.45
    194 4-fluoro-N-(7-(2-methylbenzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)benzamide Insoluble
    195 N-(3-oxo-7-(5-(pyrrolidin-1-ylmethyl)thiophen-2-yl)isoindolin-4-yl)benzamide >20
    196 N-(3-oxo-7-(5-(piperidin-1-ylmethyl)thiophen-2-yl)isoindolin-4-yl)benzamide 17.7
    197 N-(7-(5-(morpholinomethyl)thiophen-2-yl)-3-oxoisoindolin-4-yl)benzamide >20
    198 tent-butyl 4-((5-(7-benzamido-1-oxoisoindolin-4-yl)thiophen-2-yl)methyl)piperazine-1-carboxylate >20
    199 N-(7-(6-fluoropyridin-3-yl)-3-oxoisoindolin-4-yl)benzamide Insoluble
    200 N-(7-(6-methoxypyridin-3-yl)-3-oxoisoindolin-4-yl)benzamide Insoluble
    201 2-chloro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 15.2
    202 3-methoxy-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide >20
    203 N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide 0.35
    204 N-(7-(4-acetylphenyl)-3-oxoisoindolin-4-yl)-4-methoxybenzamide >20
    205 N-(7-(4-fluorophenyl)-3-oxoisoindolin-4-yl)benzamide >20
    206 N-(7-(4-(dimethylamino)phenyl)-3-oxoisoindolin-4-yl)benzamide 4.8
    207 N-(7-(4-cyanophenyl)-3-oxoisoindolin-4-yl)benzamide >20
    208 4-cyano-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide >20
    209 N-(3-oxo-7-(p-tolyl)isoindolin-4-yl)benzamide 2.8
    210 N-(3-oxo-7-(4-(trifluoromethyl)phenyl)isoindolin-4-yl)benzamide >20
    211 N-(3-oxo-7-phenylisoindolin-4-yl)isonicotinamide 0.7
    212 N-(3-oxo-7-phenylisoindolin-4-yl)furan-2-carboxamide 0.3
    213 N-(3-oxo-7-phenylisoindolin-4-yl)nicotinamide 0.6
    214 4-fluoro-N-(3-oxo-7-(quinolin-6-yl)isoindolin-4-yl)benzamide >20
    215 4-fluoro-N-(3-oxo-7-(quinolin-5-yl)isoindolin-4-yl)benzamide 0.24
    216 4-fluoro-N-(3-oxo-7-(quinolin-4-yl)isoindolin-4-yl)benzamide 0.16
    217 N-(7-(1H-indo1-7-yl)-3-oxoisoindolin-4-yl)-4-fluorobenzamide 2.95
    218 N-(7-(1H-benzo[d]imidazol-4-yl)-3-oxoisoindolin-4-yl)-4-fluorobenzamide 0.59
    219 N-(7-benzyl-3-oxoisoindolin-4-yl)-4-fluorobenzamide 13.9
    220 (R)-tent-butyl 2-((3-oxo-7-phenylisoindolin-4-yl)carbamoyl)pyrrolidine-1-carboxylate N/A
    221 (R)-N-(3-oxo-7-phenylisoindolin-4-yl)pyrrolidine-2-carboxamide N/A
    222 3-amino-N-(2-methyl-3-oxo-7-phenylisoindolin-4-yl)benzamide N/A
    223 2-amino-N-(2-methyl-3-oxo-7-phenylisoindolin-4-yl)benzamide N/A
    224 N-(7-(2,3-dimethoxyphenyl)-2-(furan-2-carbonyl)-3-oxoisoindolin-4-yl)furan-2-carboxamide 1
    225 N-(7-(2,3-dimethoxyphenyl)-3-oxo-2-(thiophene-2-carbonyl)isoindolin-4-yl)thiophene-2-carboxamide >20
    226 1-(4-fluorophenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea 2.5
    227 1-(3-oxo-7-phenylisoindolin-4-yl)-3-phenylurea 1.2
    228 1-(4-cyanophenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea >20
    229 1-butyl-3-(3-oxo-7-phenylisoindolin-4-yl)urea 1.1
    230 1-(4-methoxyphenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea 0.9
    231 1-cyclohexyl-3-(3-oxo-7-phenylisoindolin-4-yl)urea >20
    232 1-(3-oxo-7-phenylisoindolin-4-yl)-3-(p-tolyflurea 2.1
    233 1-(2-methoxyphenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea 16.7
    234 1-isopropyl-3-(3-oxo-7-phenylisoindolin-4-yl)urea 1.9
    235 1-(4-nitrophenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea 4.6
    236 1-ethyl-3-(3-oxo-7-phenylisoindolin-4-yl)urea 0.58
    237 1-(4-acetylphenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea 4.9
    238 1-(3-oxo-7-phenylisoindolin-4-yl)-3-(o-tolyl)urea >20
    239 1-cyclopentyl-3-(3-oxo-7-phenylisoindolin-4-yl)urea >20
    240 1-(3-fluorophenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea 2.4
    241 1-(3-(methylthio)phenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea 2.7
    242 1-(2-fluorophenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea 2.3
    243 1-(4-chlorophenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea 3.9
    244 1-(7-(4-methoxyphenyl)-3-oxoisoindolin-4-yl)-3-phenylurea 4.02
    245 1-(7-(4-fluorophenyl)-3-oxoisoindolin-4-yl)-3-phenylurea 6.5
    246 7-amino-N-cyclohexyl-1-oxo-4-phenylisoindolin-2-carboxamide >20
    247 1-(3-oxo-7-phenylisoindolin-4-yl)-3-phenylthiourea >20
    248 phenyl (3-oxo-7-phenylisoindolin-4-yl)carbamate >20
    249 N-(3-oxo-7-phenylisoindolin-4-yl)benzenesulfonamide >20
    250 N-(3-oxo-7-phenylisoindolin-4-yl)methanesulfonamide 21.0
    251 4-fluoro-N-(3-oxo-7-phenylisoindolin-4-yl)benzenesulfonamide >20
    252 4-methoxy-N-(3-oxo-7-phenylisoindolin-4-yl)benzenesulfonamide >20
    253 7-((2-chloroethyl)amino)-4-phenylisoindolin-1-one 2.6
    254 3-((3-oxo-7-phenylisoindolin-4-yl)amino)propanenitrile 5.6
    255 7-((2-(dimethylamino)ethyl)amino)-4-phenylisoindolin-1-one >20
    256 7-((2-hydroxyethyl)amino)-4-phenylisoindolin-1-one 4.9
    257 2-(2-((3-oxo-7-phenylisoindolin-4-yl)amino)ethyl)isoindolin-1,3-dione Insoluble
    258 7-((2-(4-methylpiperazin-1-yl)ethyl)amino)-4-phenylisoindolin-1-one >20
    259 4-phenyl-7((2-(piperidin-1-yl)ethyl)amino)isoindolin-1-one >20
    260 7-((2-morpholinoethyl)amino)-4-phenylisoindolin-1-one >20
    261 7-((2-(methylamino)ethyl)amino)-4-phenylisoindolin-1-one >20
    262 4-phenyl-7((2-(pyrrolidin-1-yl)ethyl)amino)isoindolin-1-one >20
    263 7-(benzylamino)-4-phenylisoindolin-1-one >20
    264 2-(3-((3-oxo-7-phenylisoindolin-4-yl)amino)propyl)isoindolin-1,3-dione Insoluble
    265 4-(pyridin-4-yl)-7-(pyrrolidin-1-yl)isoindolin-1-one
    266 7-(dimethylamino)-4-(2-((3-methoxyphenyl)amino)pyrimidin-4-yl)isoindolin-1-one 0.75 1.96
    267 7-(dimethylamino)-4-(2-((3-fluorophenyl)amino)pyrimidin-4-yl)isoindohn-1-one 3.98 5.51
    268 7-(butylamino)-4-(2-((3-methoxyphenyl)amino)pyrimidin-4-yll)isomdohn-1-one 0.32 0.88
    269 7-(butyl(methyl)amino)-4-(2-((3-methoxyphenyl)amino)pyrimidin-4-yl)isoindolin-1-one 2.55 5.97
    270 7-(butyl(methyl)amino)-4-(2-((3-methoxyphenyl)amino)pyrimidin-4-yl)-2-methylisoindolin-1-one >10 >10
    271 4-amino-7-phenylisoindolin-1,3-dione 2.5
    272 4-amino-7-(2-methoxyphenyl)isoindolin-1,3-dione 10.9
    273 4-amino-7-(2,3-dimethoxyphenyl)isoindolin-1,3-dione Insoluble
    274 4-amino-7-(furan-2-yl)isoindolin-1,3-dione 3.6
    275 4-amino-7-(thiophen-2-yl)isoindolin-1,3-dione 1.1
    276 N-(1,3-dioxo-7-phenylisoindolin-4-yl)benzamide 1.1
    277 N-(7-(2-methoxyphenyl)-1,3-dioxoisoindolin-4-yl)benzamide 0.65
    278 N-(7-(2,3-dimethoxyphenyl)-1,3-dioxoisoindolin-4-yl)benzamide 0.41
    279 4-fluoro-N-(3-oxo-7-phenyl-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yl)benzamide >20
    280 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide 0.073
    281 N-(7-bromo-3-oxoisoindolin-4-yl)-4-((2-(dimethylamino)ethyl)amino)benzamide 2.42
    282 N-(7-bromo-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide 1.40
    283 N-(7-bromo-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide 1.76
    284 N-(7-bromo-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide 1.55
    285 4-((2-(azep an-1-yl)ethyl)amino)-N-(7-bromo-3-oxoisoindolin-4-yl)benzamide 1.13
    286 N-(7-bromo-3-oxoisoindolin-4-yl)-4-((3-(dimethylamino)propyl)amino)benzamide 1.48
    287 N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-44(2-((2-1-yl)ethyl)amino)benzamide 0.66
    288 N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((2-methoxyethyl)amino)benzamide 0.45
    289 N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide 0.36
    290 N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((2-morpholinoethyl)amino)benzamide 0.18
    291 4-((2-(dimethylamino)ethyl)amino)-N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)benzamide 0.54
    292 N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((2-hydroxyethyl)amino)benzamide 0.47
    293 4-((2-(azepan-1-yl)ethyl)amino)-N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)benzamide 0.48
    294 N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((2-(4-methylpiperazin-1-yl)ethyl)amino)benzamide 0.23
    295 N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((3-(4-methylpiperazin-1-yl)propyl)amino)benzamide 0.52
    296 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-morpholinopropyl)amino)benzamide 0.085
    297 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-morpholinoethyl)amino)benzamide 0.075
    298 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide 0.078
    299 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide 0.05
    300 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-methoxyethyl)amino)benzamide 0.11
    301 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(dimethylamino)ethyl)amino)benzamide 0.10
    302 N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide 0.16
    303 N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide 0.30
    hydrochloride
    304 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide 0.073
    hydrochloride
    305 4-((2-(dimethylamino)ethyl)amino)-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide 0.20
    306 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-(dimethylamino)propyl)amino)benzamide 0.074
    307 N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide 0.19
    308. N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide 0.053
    309 2-methyl-N-(3-oxo-7-phenylisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide 4.82
    310 4-((3-methoxypropyl)amino)-N-(7-(2-methoxypyridin-3-yl)-3-oxoisoindolin-4-yl)benzamide 0.39
    311 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-hydroxyethyl)amino)benzamide 0.052
    312 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-morpholinobenzamide 0.73
    313 N-(7-(3-fluoro-2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide 0.45
    314 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(4-methylpiperazin-1-yl)ethyl)amino)benzamide 0.086
    315 4-((2-aminoethyl)amino)-N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide 0.037
    316 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-(4-methylpiperazin-1- 0.057
    yl)propyl)amino)benzamide
    317 N-(3-oxo-7-phenylisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide 0.36
    318 N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide 0.26
    319 4-(4-methylpiperazin-1-yl)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 2.7
    320 4-morpholino-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 8.8
    321 4-((2-methoxyethyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 0.5
    322 4-((2-morpholinoethyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 0.34
    323 N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-morpholinobenzamide 0.37
    324 4-((2-methoxyethyl)amino)-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide 0.3
    325 N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-(4-methylpiperazin-1-yl)benzamide 0.37
    326 N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-morpholinoethyl)amino)benzamide 0.093
    327 4-((3-morpholinopropyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 0.7
    328 N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-morpholinopropyl)amino)benzamide 0.4
    329 4-((3-(4-methylpiperazin-1-yl)propyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 0.44
    330 N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-(4-methylpiperazin-1-yl)propyl)amino)benzamide 0.51
    331 4-((3-methoxypropyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 0.79
    332 N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-methoxypropyl)amino)benzamide 0.51
    333 N-(3-oxo-7-phenylisoindolin-4-yl)-4-((thiophen-2-ylmethyl)amino)benzamide 1.6
    334 N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((thiophen-2-ylmethyl)amino)benzamide 0.41
    335 4-((3-(dimethylamino)propyl)amino)-N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)benzamide 0.43
    336 N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((3-methoxypropyl)amino)benzamide 0.98
    337 N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((3-morpholinopropyl)amino)benzamide 0.56
    338 N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide 0.37
    339 N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-44(3-((3-1-yl)propyl)amino)benzamide 0.31
    340 4-(4-aminopiperidin-1-yl)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 0.68
    341 N-(7-(benzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)-4-((2-(dimethylamino)ethyl)amino)benzamide 0.038
    342 N-(7-(benzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide 0.043
    343 N-(7-(benzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide 0.042
    344 4-((2-(azepan-1-yl)ethyl)amino)-N-(7-(benzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)benzamide 0.061
    345 4-(2-morpholinoethoxy)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 1.14
    346 N-(3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide 6.17
    347 N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-(2-morpholinoethoxy)benzamide 0.20
    348 N-(7-(3-amino-2-hydroxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-morpholinoethyl)amino)benzamide 3.18
    349 4-((2-(azepan-1-yl)ethyl)amino)-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide 0.24
    350 4-((2-(azepan-1-yl)ethyl)amino)-N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide 0.061
    351 4-((3-(dimethylamino)propyl)amino)-N-(7-(2-hydroxyphenyl)-3-oxoisoindolin-4-yl)benzamide 0.96
    352 4-((2-hydroxyethyl)amino)-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide 0.084
    353 4-((2-hydroxyethyl)amino)-N-(7-(2-hydroxyphenyl)-3-oxoisoindolin-4-yl)benzamide 0.37
    354 4-((3-hydroxypropyl)amino)-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide 0.22
    355 N-(7-(2-hydroxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-hydroxypropyl)amino)benzamide 0.59
    356 4-((4-hydroxybutyl)amino)-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide 0.25
    357 4-((4-hydroxybutyl)amino)-N-(7-(2-hydroxyphenyl)-3-oxoisoindolin-4-yl)benzamide 0.64
    358 4-(methyl(2-(methylamino)ethyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 1.1
    359 N-(7-(2,3-difluorophenyl)-3-oxoisoindolin-4-yl)-4-((2-morpholinoethyl)amino)benzamide 0.17
    360 N-(3-oxo-7-phenylisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide 0.32
    361 N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide 0.17
    362 4-((2-(dimethylamino)ethyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 0.49
    363 N-(3-oxo-7-phenylisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide 0.33
    364 N-(7-(2,3-difluorophenyl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide 0.18
    365 N-(7-(2,3-difluorophenyl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide 0.17
    hydrochloride
    366 N-(7-(2,3-difluorophenyl)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide 0.17
    hydrochloride
    367 N-(7-(2,3-difluorophenyl)-3-oxoisoindolin-4-yl)-4-((2-(dimethylamino)ethyl)amino)benzamide 0.28
    368 N-(7-(2,3-difluorophenyl)-3-oxoisoindolin-4-yl)-4-((3-(dimethylamino)propyl)amino)benzamide Insoluble
    369 4-((2-(azepan-1-yl)ethyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 0.56
    370 N-(3-oxo-7-phenylisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide 0.51
    371 4-((2-hydroxyethyl)amino)-N-(3-oxo-7-(thiophen-2-yl)isoindolin-4-yl)benzamide Insoluble
    372 4-((2-methoxyethyl)amino)-N-(3-oxo-7-(thiophen-2-yl)isoindolin-4-yl)benzamide 1.36
    373 4-((2-(dimethylamino)ethyl)amino)-N-(3-oxo-7-(thiophen-2-yl)isoindolin-4-yl)benzamide 0.40
    374 N-(3-oxo-7-(thiophen-2-yl)isoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide 0.48
    375 4-((2-morpholinoethyl)amino)-N-(3-oxo-7-(thiophen-2-yl)isoindolin-4-yl)benzamide 0.54
    376 N-(7-(benzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide 0.072
    377 N-(7-(2-methylbenzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide 0.36
    378 4-((2-(4-methylpiperazin-1-yl)ethyl)amino)-N-(3-oxo-7-(thiophen-2-yl)isoindolin-4-yl)benzamide 0.13
    379 4-((2-(4-methylpiperazin-1-yl)ethyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 0.35
    380 4-((2-hydroxyethyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 0.23
    381 4-((3-(dimethylamino)propyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 0.31
    382 4-((3-hydroxypropyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 0.33
    383 4-((4-hydroxybutyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide 0.38
    384 N-(7-(benzofuran-2-yl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide 1.11
    385 N-(3-oxo-7-(quinolin-6-yl)isoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide 0.78
    386 N-(3-oxo-7-(quinolin-5-yl)isoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide 0.099
    387 N-(3-oxo-7-(quinolin-4-yl)isoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide 0.033
    388 7-(4-fluorobenzamido)-1-oxoisoindoline-4-carboxylic acid 3.89
    389 7-(4-fluorobenzamido)-N-methyl-1-oxoisoindoline-4-carboxamide >20
    390 N-methyl-1-oxo-7-(4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamido)isoindoline-4-carboxamide 3.87
    391 4-fluoro-N-(3-oxo-7-(pyrrolidine-1-carbonyl)isoindolin-4-yl)benzamide >20
    392 N-(3-oxo-7-(pyrrolidine-1-carbonyl)isoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide >20
    393 4-fluoro-N-(7-(2-hydroxypropan-2-yl)-3-oxoisoindolin-4-yl)benzamide 2.57
    394 N-(7-(2-hydroxypropan-2-yl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide 5.44
    395 N-(7-cyano-3-oxoisoindolin-4-yl)-4-fluorobenzamide
    396 4-fluoro-N-(7-hydroxy-3-oxoisoindolin-4-yl)benzamide 1.29
    397 4-acetamido-N-(1-oxo-5-phenyl-1,2,3,4-tetrahydroisoquinolin-8-yl)benzamide 5.4
    398 N-(1-oxo-5-phenyl-1,2,3,4-tetrahydroisoquinolin-8-yl)benzamide 3.3
    399 N-(1-oxo-5-phenyl-1,2,3,4-tetrahydroisoquinolin-8-yl)furan-2-carboxamide 1.8
    400 N-(5-(2,3-dimethoxyphenyl)-1-oxo-1,2,3,4-tetrahydroisoquinolin-8-yl)-4-fluorobenzamide 8.18
    401 N-(1-oxo-5-phenyl-1,2,3,4-tetrahydroisoquinolin-8-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide 2.15
    402 N-(5-(2-methoxyphenyl)-1-oxo-1,2,3,4-tetrahydroisoquinolin-8-yl)-4-((2-(pyrrolidin-1- 2.38
    yl)ethyl)amino)benzamide
    403 N-(5-bromo-1-oxo-1,2,3,4-tetrahydroisoquinolin-8-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide 9.82
    404 4-fluoro-N-(3-oxo-7-(phenylthio)isoindolin-4-yl)benzamide >20
    405 N-(1-oxo-5-(phenylthio)-1,2,3,4-tetrahydroisoquinolin-8-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide 0.57
    406 N-(3-oxo-7-(phenylsulfonyl)isoindolin-4-yl)benzamide >20
    407 N-(3-oxo-7-(phenylthio)isoindolin-4-yl)benzamide 2.3
    408 4-fluoro-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide 0.28
    409 N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide 0.32
    410 N-(7-((2-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)benzamide 0.45
    411 N-(3-oxo-7-(o-tolylamino)isoindolin-4-yl)benzamide >20
    412 N-(3-oxo-7-(p-tolylamino)isoindolin-4-yl)benzamide 4.1
    413 N-(7-((2-fluorophenyl)amino)-3-oxoisoindolin-4-yl)benzamide 0.5
    414 N-(7-((4-fluorophenyl)amino)-3-oxoisoindolin-4-yl)benzamide 0.55
    415 N-(7-((3-fluorophenyl)amino)-3-oxoisoindolin-4-yl)benzamide 1.7
    416 N-(7-((4-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)benzamide 3.7
    417 4-methyl-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide 0.5
    418 N-(7-((3-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-fluorobenzamide 1.17
    419 N-(7-((2-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-fluorobenzamide 2.11
    420 2-fluoro-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide 0.79
    421 3-fluoro-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide 0.82
    422 N-(7-((2,3-dimethoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-fluorobenzamide 1.18
    423 N-(7-((3,5-bis(trifluoromethyl)phenyl)amino)-3-oxoisoindolin-4-yl)-4-fluorobenzamide >20
    424 N-(7-((2,3-dimethylphenyl)amino)-3-oxoisoindolin-4-yl)-4-fluorobenzamide 1.35
    425 4-fluoro-N-(7-((2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide 0.84
    426 4-fluoro-N-(3-oxo-7-(o-tolylamino)isoindolin-4-yl)benzamide 1.26
    427 4-fluoro-N-(3-oxo-7-(pyridin-3-ylamino)isoindolin-4-yl)benzamide 0.62
    428 4-fluoro-N-(3-oxo-7-(pyridin-2-ylamino)isoindolin-4-yl)benzamide Insoluble
    429 4-fluoro-N-(3-oxo-7-(pyrazin-2-ylamino)isoindolin-4-yl)benzamide 0.53
    430 4-fluoro-N-(7-((1-methyl-1H-pyrazol-4-yDamino)-3-oxoisoindolin-4-yl)benzamide 6.47
    431 N-(7-((3-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)benzamide 0.94
    432 2-methoxy-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide 12.2
    433 4-methoxy-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide 0.4
    434 3-methoxy-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide 0.67
    435 4-acetamido-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide 0.21
    436 N-(3-oxo-7-(m-tolylamino)isoindolin-4-yl)benzamide 0.59
    437 N-(7-((1H-pyrazol-3-yDamino)-3-oxoisoindolin-4-yl)-4-fluorobenzamide 2.9
    438 N-(3-oxo-7-(phenylamino)isoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide 0.16
    439 N-(3-oxo-7-(phenylamino)isoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide 0.15
    440 N-(3-oxo-7-(phenylamino)isoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide hydrochloride —
    441 4-((2-(dimethylamino)ethyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide 0.24
    442 4-((2-morpholinoethyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide 0.15
    443 4-((2-(4-methylpiperazin-1-yl)ethyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide 0.12
    444 4-((2-methoxyethyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide 0.11
    445 N-(7-((3-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide 0.55
    446 N-(7-((3-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide 0.63
    447 N-(7-((3-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide 0.55
    448 N-(7-((3-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide 0.62
    449 N-(3-oxo-7-(m-tolylamino)isoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide 0.59
    450 N-(3-oxo-7-(m-tolylamino)isoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide 0.58
    451 N-(3-oxo-7-(m-tolylamino)isoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide 0.48
    452 N-(3-oxo-7-(m-tolylamino)isoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide 0.44
    453 N-(7-((2-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide 0.51
    454 N-(7-((2-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide 0.53
    455 N-(7-((3-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide 0.20
    456 N-(7-((3-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide 0.34
    457 N-(7-((3-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide 0.15
    458 N-(7-((3-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide 0.24
    459 N-(3-oxo-7-(phenylamino)isoindolin-4-yl)-4-((3-(2-oxopyrrolidin-1-yl)propyl)amino)benzamide 0.21
    460 4-((3-(dimethylamino)propyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide 0.14
    461 4-((3-morpholinopropyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide 0.38
    462 N-(3-oxo-7-(phenylamino)isoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide 0.29
    463 4-((3-(4-methylpiperazin-1-yl)propyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide 0.37
    464 4-((3-hydroxypropyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide 0.074
    465 N-(7-((3,5-bis(trifluoromethyl)phenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1- >20
    yl)ethyl)amino)benzamide
    466 N-(7-((3,5-bis(trifluoromethyl)phenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1- 14
    yl)propyl)amino)benzamide
    467 N-(7-((3,5-bis(trifluoromethyl)phenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1- >20
    yl)ethyl)amino)benzamide
    468 N-(7-((3,5-bis(trifluoromethyl)phenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1- 17.11
    yl)propyl)amino)benzamide
    469 N-(7-((2,3-dimethylphenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide 0.37
    470 N-(7-((2,3-dimethylphenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide 0.47
    471 N-(7-((2,3-dimethylphenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide 0.61
    472 N-(7-((2,3-dimethylphenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide 0.41
    473 N-(3-oxo-7-(o-tolylamino)isoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide 0.43
    474 N-(7-((2-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide 0.44
    475 N-(7-((2-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide 0.47
    476 N-(3-oxo-7-(o-tolylamino)isoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide 0.50
    477 N-(7-((2-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide 0.42
    478 N-(7-((2-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide 0.49
    479 N-(3-oxo-7-(phenylamino)isoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide 0.11
    480 N-(3-oxo-7-(phenylamino)isoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide hydrochloride 0.22
    481 4-((2-aminoethyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide 0.20
    482 N-(3-oxo-7-(o-tolylamino)isoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide 0.42
    483 N-(3-oxo-7-(o-tolylamino)isoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide 0.25
    484 4-((4-hydroxybutyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide 0.29
    485 4-((2-acetamidoethyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide 0.10
    486 4-((3-aminopropyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide 0.2
    487 4-((2-hydroxyethyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide 0.097
    488 4-((2-hydroxy-3-(piperidin-1-yl)propyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide 0.093
    489 (S)-4-((2-hydroxy-3-(piperidin-1-yl)propyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide 0.087
    490 (R)-4-((2-hydroxy-3-(piperidin-1-yl)propyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide 0.14
    491 4-(4-aminopiperidin-1-yl)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide 0.11
    492 4-((2-(azepan-1-yl)ethyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide 0.18

Claims (28)

1. A compound selected from the group consisting of a compound of formula (I), a pharmaceutically acceptable salt, a hydrate, and a solvate thereof:
Figure US20160311772A1-20161027-C00530
wherein,
X is CH or N;
Y is CH2 or C(═O);
n is 1 or 2;
R1 is 5- to 10-membered heterocycloalkyl, —NH2, —NH—C(═O)—R4, —NH—C(═O)—NH—R5, —NH—C(═O)—O—R6, —NH—C(═S)—NH—R7, —NH—S(═O)2—R8, —NH—R9-R10, or —N—R11)—R12;
R2 is H, halogen, cyano, hydroxy, benzyl, C1-7 alkyl, substituted or unsubstituted C6-14 aryl, substituted or unsubstituted 5- to 13-membered heteroaryl, substituted or unsubstituted C3-10 cycloalkyl, —C(═O)—R13, —C(═O)—NH—R14, hydroxy-(C1-7 alkyl), —S—R15, —S(═O)2—R16 or —NH—R17; and
R3 is H, C1-7 alkyl, —C(═O)—R18 or —C(═O)—NH—R19;
wherein,
R4 to R8 are each independently C1-7 alkyl, substituted or unsubstituted C6-14 aryl, substituted or unsubstituted 5- to 13-membered heteroaryl, substituted or unsubstituted C3-10 cycloalkyl or substituted or unsubstituted 5- to 10-membered heterocycloalkyl;
R9 is C1-7 alkyl;
R10 is H, hydroxy, halogen, cyano, C1-7 alkyl, (C1-7 alkyl)amino, (diC1-7 alkyl)amino, substituted or unsubstituted C6-14 aryl, substituted or unsubstituted 5- to 13-membered heteroaryl or substituted or unsubstituted 5- to 10-membered heterocycloalkyl;
R11 and R12 are each independently C1-7 alkyl;
R13 and R14 are each independently hydroxy, C1-7 alkyl, or 5- to 10-membered heterocycloalkyl;
R15 to R17 are each independently substituted or unsubstituted C6-14 aryl or substituted or unsubstituted 5- to 13-membered heteroaryl;
R18 is 5- to 13-membered heteroaryl;
R19 is C3-10 cycloalkyl; and
said cycloalkyl, heterocycloalkyl, aryl or heteroaryl is optionally substituted with one or more substituents selected from the group consisting of C1-7 alkyl; —OCF3; C1-7 alkoxy; (C1-7 alkoxy)carbonyl; (C1-7 alkyl)carbonyl; C6-14 aryl; (C1-7 alkyl)thio; halogen; (C1-7 alkyl)sulfonyl; —NH—R20-R21; —N(CH3)—R20-R21; 5- to 13-membered heteroaryl; 5- to 10-membered heterocycloalkyl unsubstituted or substituted with C1-7 alkyl or amino; (C1-7 alkylcarbonylamino)(C6-14 aryl); (5- to 10-membered heterocycloalkyl)-(C1-7 alkyl)-(5- to 13-membered heteroaryl); —CF3; cyano; (C1-7 alkyl)amino; nitro; oxo; (5- to 10-membered heterocycloalkyl)-(C1-7 alkoxy); (diC1-7 alkyl)amino; (C1-7 alkyl)carbonylamino; hydroxy; (5- to 10-membered heterocycloalkyl)-(C1-7 alkyl); (tertbutoxycarbonyl)-(5- to 10-membered heterocycloalkyl)-(C1-7 alkyl); benzyl; and amino, wherein R20 is C6-14 aryl, 5- to 13-membered heteroaryl or C1-7 alkyl which is unsubstituted or substituted with hydroxy; and R21 is 5- to 10-membered heteroaryl or 5- to 10-membered heterocycloalkyl which is unsubstituted or substituted with H, hydroxy, halogen, amino, C1-7 alkyl, (diC1-7 alkyl)amino, C1-7 alkylcarbonylamino, C1-7 alkoxy, methyl or oxo.
2. The compound of claim 1, wherein R1 is pyrrolidine.
3. The compound of claim 1, wherein R1 is —NH—C(═O)—R4, R4 being C1-4 alkyl, substituted or unsubstituted phenyl, substituted or unsubstituted thiophenyl, substituted or unsubstituted furanyl, substituted or unsubstituted pyridinyl or substituted or unsubstituted pyrrolidinyl.
4. The compound of claim 3, wherein said phenyl, thiophenyl, furanyl, pyridinyl or pyrrolidinyl is substituted with one or more substituents selected from the group consisting of fluoro, chloro, bromo, nitro, cyano, amino, tertbutyloxycarbonyl, methyl, methylthio, methylsulfonyl, methoxy, acetamido, methylpiperazinyl, aminopiperidinyl, morpholino, morpholinoethoxy, methylamino, dimethylamino, dimethylaminoethylamino, dimethylaminopropylamino, aminoethylamino, hydroxyethylamino, hydroxypropylamino, hydroxybutylamino, methoxyethylamino, methoxypropylamino, methyl(2-(methylamino)ethyl)amino, acetamidoethylamino, pyrrolidinylethylamino, pyrrolidinylpropylamino, piperidinylethylamino, piperidinylpropylamino, azepanylethylamino, morpholinoethylamino, morpholinopropylamino, methylpiperazinylethylamino, methylpiperazinylpropylamino, thiophenylmethylamino, oxopyrrolidinylpropylamino, and (2-hydroxy-3-(piperidinyl)propyl)amino.
5. The compound of claim 1, wherein R1 is —NH—C(═O)—NH—R5, R5 being methyl, ethyl, butyl, isopropyl, cyclopentyl, cyclohexyl or substituted or unsubstituted phenyl; and
said phenyl is optionally substituted with one or more substituents selected from the group consisting of fluoro, chloro, cyano, nitro, methyl, methylthio and methoxy.
6. The compound of claim 1, wherein R1 is —NH—C(═O)—O—R6, R6 being phenyl.
7. The compound of claim 1, wherein R1 is —NH—C(═S)—NH—R7, R7 being phenyl.
8. The compound of claim 1, wherein R1 is —NH—S(═O)2—R8, R8 being phenyl, methyl, fluorophenyl or methoxyphenyl.
9. The compound of claim 1, wherein R1 is —NH—R9-R10, R9 being methyl, ethyl, propyl or butyl, and R10 being H, hydroxy, chloro, cyano, methylamino, dimethylamino, phenyl, isoindolindione, methylpiperazinyl, piperidinyl, morpholino or pyrrolidine.
10. The compound of claim 1, wherein R1 is —N(—R11)—R12, R11 being methyl, and R12 being methyl or butyl.
11. The compound of claim 1, wherein R2 is substituted or unsubstituted phenyl, thiazolyl, pyrazolyl, imidazolyl, triazolyl, pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, pyrimidinyl, thiophenyl, furanyl, benzo[d]oxazol-7-yl, quinolinyl, indolyl, benzo[d]imidazolyl or benzofuranyl.
12. The compound of claim 1, wherein R2 is selected from the group consisting of H; halogen; cyano; hydroxy; C1-4 alkyl; C3-5 cycloalkyl; phenyl being unsubstituted or substituted with one or more substituents selected from the group consisting of hydroxy, cyano, amino, dimethylamino, ethyl, propyl, isopropyl, tertbutyl, acetyl, trifluoromethoxy, isopropoxy, methoxycarbonyl, methylthio, fluoro, methyl, chloro, methoxy, ethoxy, propoxy, butoxy, methylsulfonyl, —CF3, —O—CF3, and acetamido; thiazolyl; pyrazolyl; methylpyrazolyl; imidazolyl; methylimidazolyl; triazolyl; methyltriazolyl; pyridinyl; chloropyridinyl; fluoropyridinyl; methoxyphenylaminopyridinyl; methoxypyridinyl; phenyl-1H-pyrrolo[2,3-b]pyridinyl; 1H-pyrrolo[2,3-b]pyridinyl; acetamidophenyl-1H-pyrrolo[2,3-b]pyridinyl; morpholinomethylthiophenyl-1H-pyrrolo[2,3-b]pyridinyl; pyrimidinyl; dichloropyrimidinyl; methoxyphenylaminopyrimidinyl; methylpyrazolylaminopyrimidinyl; phenylaminopyrimidinyl; fluorophenylaminopyrimidinyl; acetamidophenylaminopyrimidinyl; methylpiperazinylpyrimidinyl; morpholinopyrimidinyl; tolylaminopyrimidinyl; chloropyrimidinyl; thiophenyl; pyrrolidinylmethylthiophenyl; piperidinylmethylthiophenyl; morpholinomethylthiophenyl; tertbutyloxycarbonylpiperazinylmethylthiophenyl; furanyl; benzo[d]oxazol-7-yl; methyl-benzo[d]oxazol-7-yl; quinolinyl; indolyl; benzo[d]imidazolyl; benzofuranyl; —C(═O)—R13; —C(═O)—NH—R14; hydroxy-(C1-7 alkyl); —S—R15; —S(═O)2—R16; and —NH—R17, R13 being hydroxy, methoxy or pyrrolidinyl, R14 being methyl, R15 being phenyl, R16 being phenyl, and R17 being phenyl, methoxyphenyl, methylphenyl, fluorophenyl, chlorophenyl, dimethoxyphenyl, bis(trifluoromethyl)phenyl, dimethylphenyl, pyridinyl, pyrazinyl, methylpyrazolyl or pyrazolyl.
13. The compound of claim 1, wherein R3 is methyl, —C(═O)—R18 or —C(═O)—NH—R19, R18 being furanyl or thiophenyl, and R19 being cyclohexyl.
14. The compound of claim 1, which is selected from the group consisting of:
(1) N-(7-(2-ethylphenyl)-3-oxoisoindolin-4-yl)benzamide;
(2) N-(7-(3-isopropylphenyl)-3-oxoisoindolin-4-yl)benzamide;
(3) N-(7-(4-(tert-butyl)phenyl)-3-oxoisoindolin-4-yl)benzamide;
(4) N-(3-oxo-7-(2-(trifluoromethoxy)phenyl)isoindolin-4-yl)benzamide;
(5) N-(3-oxo-7-(3-(trifluoromethoxy)phenyl)isoindolin-4-yl)benzamide;
(6) N-(7-(2-isopropoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(7) N-(7-(3-isopropoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(8) methyl 2-(7-benzamido-1-oxoisoindolin-4-yl)benzoate;
(9) methyl 3-(7-benzamido-1-oxoisoindolin-4-yl)benzoate;
(10) methyl 4-(7-benzamido-1-oxoisoindolin-4-yl)benzoate;
(11) N-(7-(2-acetylphenyl)-3-oxoisoindolin-4-yl)benzamide;
(12) N-(7-(3-acetylphenyl)-3-oxoisoindolin-4-yl)benzamide;
(13) N-(7-(4-acetylphenyl)-3-oxoisoindolin-4-yl)benzamide;
(14) N-(7-(2-(methylthio)phenyl)-3-oxoisoindolin-4-yl)benzamide;
(15) N-(7-(2,4-difluorophenyl)-3-oxoisoindolin-4-yl)benzamide;
(16) N-(7-(2,3-dimethylphenyl)-3-oxoisoindolin-4-yl)benzamide;
(17) N-(7-(2,3-dichlorophenyl)-3-oxoisoindolin-4-yl)benzamide;
(18) N-(7-(2,4-dichlorophenyl)-3-oxoisoindolin-4-yl)benzamide;
(19) N-(7-(2,5-dichlorophenyl)-3-oxoisoindolin-4-yl)benzamide;
(20) N-(7-(3,4-dichlorophenyl)-3-oxoisoindolin-4-yl)benzamide;
(21) N-(7-(3,5-dichlorophenyl)-3-oxoisoindolin-4-yl)benzamide;
(22) N-(7-(4-fluoro-2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(23) N-(7-(2-chloro-3-fluorophenyl)-3-oxoisoindolin-4-yl)benzamide;
(24) N-(7-(2-fluoro-3-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(25) N-(3-oxo-7-(2,3,4-trimethoxyphenyl)isoindolin-4-yl)benzamide;
(26) N-(7-(3,4-dimethylphenyl)-3-oxoisoindolin-4-yl)benzamide;
(27) N-(7-(3,5-dimethylphenyl)-3-oxoisoindolin-4-yl)benzamide;
(28) N-(7-(2,6-dimethylphenyl)-3-oxoisoindolin-4-yl)benzamide;
(29) N-(7-ethyl-3-oxoisoindolin-4-yl)benzamide;
(30) N-(7-(3,5-difluorophenyl)-3-oxoisoindolin-4-yl)benzamide;
(31) N-(7-(2,5-dimethylphenyl)-3-oxoisoindolin-4-yl)benzamide;
(32) N-(7-(2,5-difluorophenyl)-3-oxoisoindolin-4-yl)benzamide;
(33) N-(7-(3,4-difluorophenyl)-3-oxoisoindolin-4-yl)benzamide;
(34) N-(7-(2,3-difluorophenyl)-3-oxoisoindolin-4-yl)benzamide;
(35) N-(7-butyl-3-oxoisoindolin-4-yl)benzamide;
(36) 4-fluoro-N-(3-oxo-7-propylisoindolin-4-yl)benzamide;
(37) N-(7-methyl-3-oxoisoindolin-4-yl)benzamide;
(38) N-(7-(2,4-dimethylphenyl)-3-oxoisoindolin-4-yl)benzamide;
(39) N-(7-(4-ethylphenyl)-3-oxoisoindolin-4-yl)benzamide;
(40) N-(7-(4-isopropoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(41) N-(7-(4-(methylthio)phenyl)-3-oxoisoindolin-4-yl)benzamide;
(42) N-(7-(3-ethylphenyl)-3-oxoisoindolin-4-yl)benzamide;
(43) N-(3-oxo-7-(2-propoxyphenyl)isoindolin-4-yl)benzamide;
(44) N-(3-oxo-7-(3-propoxyphenyl)isoindolin-4-yl)benzamide;
(45) N-(7-(2-butoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(46) N-(7-(3-butoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(47) N-(7-(2-(methylsulfonyl)phenyl)-3-oxoisoindolin-4-yl)benzamide;
(48) N-(7-(3-fluoro-2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(49) N-(7-(4-chloro-2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(50) N-(7-(3-chloro-2-fluorophenyl)-3-oxoisoindolin-4-yl)benzamide;
(51) N-(3-oxo-7-(thiazol-5-yl)isoindolin-4-yl)benzamide;
(52) N-(3-oxo-7-(thiazol-4-yl)isoindolin-4-yl)benzamide;
(53) N-(3-oxo-7-(thiazol-2-yl)isoindolin-4-yl)benzamide;
(54) N-(7-(1H-imidazol-4-yl)-3-oxoisoindolin-4-yl)benzamide;
(55) N-(3-oxo-7-(1H-pyrazol-4-yl)isoindolin-4-yl)benzamide;
(56) N-(7-(1-methyl-1H-imidazol-5-yl)-3-oxoisoindolin-4-yl)benzamide;
(57) N-(7-(1-methyl-1H-pyrazol-4-yl)-3-oxoisoindolin-4-yl)benzamide;
(58) N-(3-oxo-7-(1H-1,2,4-triazol-5-yl)isoindolin-4-yl)benzamide;
(59) N-(7-(1-methyl-1H-1,2,4-triazol-5-yl)-3-oxoisoindolin-4-yl)benzamide;
(60) 7-amino-4-(4-methoxyphenyl)isoindolin-1-one;
(61) 7-amino-4-(4-fluorophenyl)isoindolin-1-one;
(62) 7-amino-4-(4-chlorophenyl)isoindolin-1-one;
(63) 7-amino-4-(p-tolyl)isoindolin-1-one;
(64) 4-(4-acetylphenyl)-7-aminoisoindolin-1-one;
(65) 7-amino-4-(pyridin-4-yl)isoindolin-1-one;
(66) 7-amino-4-(2,6-dichloropyrimidin-4-yl)isoindolin-1-one;
(67) 7-amino-4-(2-chloropyrimidin-4-yl)isoindolin-1-one;
(68) 7-amino-4-(2-((3-methoxyphenyl)amino)pyridin-4-yl)isoindolin-1-one;
(69) 7-amino-4-(4-((3-methoxyphenyl)amino)pyridin-2-yl)isoindolin-1-one;
(70) 7-amino-4-(2-((3-methoxyphenyl)amino)pyrimidin-4-yl)isoindolin-1-one;
(71) 7-amino-4-(2-((l-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)isoindolin-1-one;
(72) 7-amino-4-(2-(phenylamino)pyrimidin-4-yl)isoindolin-1-one;
(73) 7-amino-4-(2-((3-fluorophenyl)amino)pyrimidin-4-yl)isoindolin-1-one;
(74) 7-amino-4-(2-((4-fluorophenyl)amino)pyrimidin-4-yl)isoindolin-1-one;
(75) 7-amino-4-(2-((4-methoxyphenyl)amino)pyrimidin-4-yl)isoindolin-1-one;
(76) N-(4-((4-(7-amino-1-oxoisoindolin-4-yl)pyrimidin-2-yl)amino)phenyl)acetamide;
(77) N-(3-((4-(7-amino-1-oxoisoindolin-4-yl)pyrimidin-2-yl)amino)phenyl)acetamide;
(78) 7-amino-4-(6-((3-methoxyphenyl)amino)pyrimidin-4-yl)isoindolin-1-one;
(79) 7-amino-4-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)isoindolin-1-one;
(80) 7-amino-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)isoindolin-1-one;
(81) 7-amino-4-(2-(4-methylpiperazin-1-yl)pyrimidin-4-yl)isoindolin-1-one;
(82) 7-amino-4-(2-morpholinopyrimidin-4-yl)isoindolin-1-one;
(83) 7-amino-4-(2-(p-tolylamino)pyrimidin-4-yl)isoindolin-1-one;
(84) 7-amino-4-(2-(m-tolylamino)pyrimidin-4-yl)isoindolin-1-one;
(85) N-(4-(3-(7-amino-1-oxoisoindolin-4-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)acetamide;
(86) 7-amino-4-(5-(5-(morpholinomethyl)thiophen-2-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)isoindolin-1-one;
(87) 2-methyl-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(88) 3-methyl-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(89) 4-methyl-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(90) 3-chloro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(91) 2,4-difluoro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(92) 3,4-difluoro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(93) 3,4-dimethyl-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(94) 2-(dimethylamino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(95) 3-(dimethylamino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(96) 2-(methylthio)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(97) 3-(methylthio)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(98) 2-(methylsulfonyl)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(99) 3-(methylsulfonyl)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(100) 4-(methylsulfonyl)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(101) 2,4-dimethoxy-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(102) 3,4-dimethoxy-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(103) 2,4-dichloro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(104) 3,4-dichloro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(105) 2,4-dimethyl-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(106) 2-acetamido-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(107) 3-acetamido-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(108) 4-(methylamino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(109) 3-methyl-N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide;
(110) 4-methyl-N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide;
(111) 5-methyl-N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide;
(112) N-(3-oxo-7-(o-tolyl)isoindolin-4-yl)benzamide;
(113) N-(3-oxo-7-(m-tolyl)isoindolin-4-yl)benzamide;
(114) N-(3-oxo-7-(2-(trifluoromethyl)phenyl)isoindolin-4-yl)benzamide;
(115) N-(3-oxo-7-(3-(trifluoromethyl)phenyl)isoindolin-4-yl)benzamide;
(116) 4-acetamido-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(117) N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(118) N-(7-(4-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(119) 4-nitro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(120) 4-acetamido-N-(7-(4-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(121) 4-methoxy-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(122) 4-fluoro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(123) N-(7-(4-fluorophenyl)-3-oxoisoindolin-4-yl)-4-methoxybenzamide;
(124) 4-acetamido-N-(7-(4-fluorophenyl)-3-oxoisoindolin-4-yl)benzamide;
(125) N-(3-oxo-7-(thiophen-2-yl)isoindolin-4-yl)benzamide;
(126) N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)benzamide;
(127) N-(3-oxo-7-(pyridin-4-yl)isoindolin-4-yl)benzamide;
(128) N-(3-oxo-7-(pyridin-4-yl)isoindolin-4-yl)benzamide hydrochloride;
(129) 2-methoxy-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(130) 3-fluoro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(131) 4-(methylthio)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(132) N-(3-oxo-7-(4-propoxyphenyl)isoindolin-4-yl)benzamide;
(133) N-(7-(4-isopropylphenyl)-3-oxoisoindolin-4-yl)benzamide;
(134) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)furan-2-carboxamide;
(135) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-fluorobenzamide;
(136) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)thiophene-2-carboxamide;
(137) 4-fluoro-2-methyl-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(138) 4-acetamido-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(139) 4-(dimethylamino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(140) 4-acetamido-N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)benzamide;
(141) 4-fluoro-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(142) 2-fluoro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(143) 4-chloro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(144) N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(145) N-(7-(3-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(146) N-(3-oxo-7-(thiophen-3-yl)isoindolin-4-yl)benzamide;
(147) N-(7-(3-cyanophenyl)-3-oxoisoindolin-4-yl)benzamide;
(148) N-(7-(3-(dimethylamino)phenyl)-3-oxoisoindolin-4-yl)benzamide;
(149) N-(7-(2-fluorophenyl)-3-oxoisoindolin-4-yl)benzamide;
(150) N-(7-(furan-3-yl)-3-oxoisoindolin-4-yl)benzamide;
(151) N-(7-(3-fluorophenyl)-3-oxoisoindolin-4-yl)benzamide;
(152) N-(3-oxo-7-(pyridin-3-yl)isoindolin-4-yl)benzamide;
(153) N-(3-oxo-7-(pyridin-3-yl)isoindolin-4-yl)benzamide hydrochloride;
(154) N-(3-oxo-7-(pyrimidin-5-yl)isoindolin-4-yl)benzamide;
(155) 3-chloro-N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide;
(156) 5-bromo-N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide;
(157) 3-bromo-N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide;
(158) 4-fluoro-N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)benzamide;
(159) N-(3-oxo-7-phenylisoindolin-4-yl)pentanamide;
(160) N-(3-oxo-7-phenylisoindolin-4-yl)acetamide;
(161) N-(7-(2-chloropyrimidin-4-yl)-3-oxoisoindolin-4-yl) acetamide;
(162) N-(7-(2-((3-methoxyphenyl)amino)pyrimidin-4-yl)-3-oxoisoindolin-4-yl) acetamide;
(163) N-(7-(2-((3-fluorophenyl)amino)pyrimidin-4-yl)-3-oxoisoindolin-4-yl) acetamide;
(164) N-(3-oxo-7-(2-(m-tolylamino)pyrimidin-4-yl)isoindolin-4-yl)acetamide;
(165) N-(3-oxo-7-(2-(p-tolylamino)pyrimidin-4-yl)isoindolin-4-yl)acetamide;
(166) N-(7-(2-((3-methoxyphenyl)amino)pyrimidin-4-yl)-3-oxoisoindolin-4-yl)propionamide;
(167) N-(7-(4-(methylsulfonyl)phenyl)-3-oxoisoindolin-4-yl)benzamide;
(168) N-(7-(3-(methylsulfonyl)phenyl)-3-oxoisoindolin-4-yl)benzamide;
(169) N-(7-(3-acetamidophenyl)-3-oxoisoindolin-4-yl)benzamide;
(170) 5-chloro-N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide;
(171) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(172) N-(7-(3,5-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(173) N-(7-cyclopropyl-3-oxoisoindolin-4-yl)benzamide;
(174) N-(7-(2-chlorophenyl)-3-oxoisoindolin-4-yl)benzamide;
(175) N-(7-(2,4-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(176) N-(7-(3,4-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(177) N-(7-(3-ethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(178) N-(7-(2,5-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(179) N-(7-(4-chlorophenyl)-3-oxoisoindolin-4-yl)benzamide;
(180) N-(7-(3-chlorophenyl)-3-oxoisoindolin-4-yl)benzamide;
(181) N-(7-(4-ethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(182) N-(7-(2-ethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(183) N-(7-(2-cyanophenyl)-3-oxoisoindolin-4-yl)benzamide;
(184) N-(7-(4-butoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(185) N-(7-(2-(dimethylamino)phenyl)-3-oxoisoindolin-4-yl)benzamide;
(186) N-(3-oxo-7-(4-(trifluoromethoxy)phenyl)isoindolin-4-yl)benzamide;
(187) N-(7-(2,6-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(188) N-(3-oxo-7-(4-propylphenyl)isoindolin-4-yl)benzamide;
(189) N-(7-(2,3-dihydroxyphenyl)-3-oxoisoindolin-4-yl)-4-fluorobenzamide;
(190) 4-fluoro-N-(7-(2-hydroxy-3-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(191) 4-fluoro-N-(3-oxo-7-(thiophen-2-yl)isoindolin-4-yl)benzamide;
(192) 5-methyl-N-(3-oxo-7-phenylisoindolin-4-yl)furan-2-carboxamide;
(193) N-(7-(benzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)-4-fluorobenzamide;
(194) 4-fluoro-N-(7-(2-methylbenzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)benzamide;
(195) N-(3-oxo-7-(5-(pyrrolidin-1-ylmethyl)thiophen-2-yl)isoindolin-4-yl)benzamide;
(196) N-(3-oxo-7-(5-(piperidin-1-ylmethyl)thiophen-2-yl)isoindolin-4-yl)benzamide;
(197) N-(7-(5-(morpholinomethyl)thiophen-2-yl)-3-oxoisoindolin-4-yl)benzamide;
(198) tert-butyl 4-((5-(7-benzamido-1-oxoisoindolin-4-yl)thiophen-2-yl)methyl)piperazine-1-carboxylate;
(199) N-(7-(6-fluoropyridin-3-yl)-3-oxoisoindolin-4-yl)benzamide;
(200) N-(7-(6-methoxypyridin-3-yl)-3-oxoisoindolin-4-yl)benzamide;
(201) 2-chloro-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(202) 3-methoxy-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(203) N-(3-oxo-7-phenylisoindolin-4-yl)thiophene-2-carboxamide;
(204) N-(7-(4-acetylphenyl)-3-oxoisoindolin-4-yl)-4-methoxybenzamide;
(205) N-(7-(4-fluorophenyl)-3-oxoisoindolin-4-yl)benzamide;
(206) N-(7-(4-(dimethylamino)phenyl)-3-oxoisoindolin-4-yl)benzamide;
(207) N-(7-(4-cyanophenyl)-3-oxoisoindolin-4-yl)benzamide;
(208) 4-cyano-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(209) N-(3-oxo-7-(p-tolyl)isoindolin-4-yl)benzamide;
(210) N-(3-oxo-7-(4-(trifluoromethyl)phenyl)isoindolin-4-yl)benzamide;
(211) N-(3-oxo-7-phenylisoindolin-4-yl)isonicotinamide;
(212) N-(3-oxo-7-phenylisoindolin-4-yl)furan-2-carboxamide;
(213) N-(3-oxo-7-phenylisoindolin-4-yl)nicotinamide;
(214) 4-fluoro-N-(3-oxo-7-(quinolin-6-yl)isoindolin-4-yl)benzamide;
(215) 4-fluoro-N-(3-oxo-7-(quinolin-5-yl)isoindolin-4-yl)benzamide;
(216) 4-fluoro-N-(3-oxo-7-(quinolin-4-yl)isoindolin-4-yl)benzamide;
(217) N-(7-(1H-indol-7-yl)-3-oxoisoindolin-4-yl)-4-fluorobenzamide;
(218) N-(7-(1H-benzo[d]imidazol-4-yl)-3-oxoisoindolin-4-yl)-4-fluorobenzamide;
(219) N-(7-benzyl-3-oxoisoindolin-4-yl)-4-fluorobenzamide;
(220) (R)-tert-butyl 2-((3-oxo-7-phenylisoindolin-4-yl)carbamoyl)pyrrolidine-1-carboxylate;
(221) (R)—N-(3-oxo-7-phenylisoindolin-4-yl)pyrrolidine-2-carboxamide;
(222) 3-amino-N-(2-methyl-3-oxo-7-phenylisoindolin-4-yl)benzamide;
(223) 2-amino-N-(2-methyl-3-oxo-7-phenylisoindolin-4-yl)benzamide;
(224) N-(7-(2,3-dimethoxyphenyl)-2-(furan-2-carbonyl)-3-oxoisoindolin-4-yl)furan-2-carboxamide;
(225) N-(7-(2,3-dimethoxyphenyl)-3-oxo-2-(thiophene-2-carbonyl)isoindolin-4-yl)thiophene-2-carboxamide;
(226) 1-(4-fluorophenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea;
(227) 1-(3-oxo-7-phenylisoindolin-4-yl)-3-phenylurea;
(228) 1-(4-cyanophenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea;
(229) 1-butyl-3-(3-oxo-7-phenylisoindolin-4-yl)urea;
(230) 1-(4-methoxyphenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea;
(231) 1-cyclohexyl-3-(3-oxo-7-phenylisoindolin-4-yl)urea;
(232) 1-(3-oxo-7-phenylisoindolin-4-yl)-3-(p-tolyl)urea;
(233) 1-(2-methoxyphenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea;
(234) 1-isopropyl-3-(3-oxo-7-phenylisoindolin-4-yl)urea;
(235) 1-(4-nitrophenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea;
(236) 1-ethyl-3-(3-oxo-7-phenylisoindolin-4-yl)urea;
(237) 1-(4-acetylphenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea;
(238) 1-(3-oxo-7-phenylisoindolin-4-yl)-3-(o-tolyl)urea;
(239) 1-cyclopentyl-3-(3-oxo-7-phenylisoindolin-4-yl)urea;
(240) 1-(3-fluorophenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea;
(241) 1-(3-(methylthio)phenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea;
(242) 1-(2-fluorophenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea;
(243) 1-(4-chlorophenyl)-3-(3-oxo-7-phenylisoindolin-4-yl)urea;
(244) 1-(7-(4-methoxyphenyl)-3-oxoisoindolin-4-yl)-3-phenylurea;
(245) 1-(7-(4-fluorophenyl)-3-oxoisoindolin-4-yl)-3-phenylurea;
(246) 7-amino-N-cyclohexyl-1-oxo-4-phenylisoindolin-2-carboxamide;
(247) 1-(3-oxo-7-phenylisoindolin-4-yl)-3-phenylthiourea;
(248) phenyl (3-oxo-7-phenylisoindolin-4-yl)carbamate;
(249) N-(3-oxo-7-phenylisoindolin-4-yl)benzenesulfonamide;
(250) N-(3-oxo-7-phenylisoindolin-4-yl)methanesulfonamide;
(251) 4-fluoro-N-(3-oxo-7-phenylisoindolin-4-yl)benzenesulfonamide;
(252) 4-methoxy-N-(3-oxo-7-phenylisoindolin-4-yl)benzenesulfonamide;
(253) 7-((2-chloroethyl)amino)-4-phenylisoindolin-1-one;
(254) 3-((3-oxo-7-phenylisoindolin-4-yl)amino)propanenitrile;
(255) 7-((2-(dimethylamino)ethyl)amino)-4-phenylisoindolin-1-one;
(256) 7-((2-hydroxyethyl)amino)-4-phenylisoindolin-1-one;
(257) 2-(2-((3-oxo-7-phenylisoindolin-4-yl)amino)ethyl)isoindolin-1,3-dione;
(258) 7-((2-(4-methylpiperazin-1-yl)ethyl)amino)-4-phenylisoindolin-1-one;
(259) 4-phenyl-7-((2-(piperidin-1-yl)ethyl)amino)isoindolin-1-one;
(260) 7-((2-morpholinoethyl)amino)-4-phenylisoindolin-1-one;
(261) 7-((2-(methylamino)ethyl)amino)-4-phenylisoindolin-1-one;
(262) 4-phenyl-7-((2-(pyrrolidin-1-yl)ethyl)amino)isoindolin-1-one;
(263) 7-(benzylamino)-4-phenylisoindolin-1-one;
(264) 2-(3-((3-oxo-7-phenylisoindolin-4-yl)amino)propyl)isoindolin-1,3-dione;
(265) 4-(pyridin-4-yl)-7-(pyrrolidin-1-yl)isoindolin-1-one;
(266) 7-(dimethylamino)-4-(2-((3-methoxyphenyl)amino)pyrimidin-4-yl)isoindolin-1-one;
(267) 7-(dimethylamino)-4-(2-((3-fluorophenyl)amino)pyrimidin-4-yl)isoindolin-1-one;
(268) 7-(butylamino)-4-(2-((3-methoxyphenyl)amino)pyrimidin-4-yl)isoindolin-1-one;
(269) 7-(butyl(methyl)amino)-4-(2-((3-methoxyphenyl)amino)pyrimidin-4-yl)isoindolin-1-one;
(270) 7-(butyl(methyl)amino)-4-(2-((3-methoxyphenyl)amino)pyrimidin-4-yl)-2-methylisoindolin-1-one;
(271) 4-amino-7-phenylisoindolin-1,3-dione;
(272) 4-amino-7-(2-methoxyphenyl)isoindolin-1,3-dione;
(273) 4-amino-7-(2,3-dimethoxyphenyl)isoindolin-1,3-dione;
(274) 4-amino-7-(furan-2-yl)isoindolin-1,3-dione;
(275) 4-amino-7-(thiophen-2-yl)isoindolin-1,3-dione;
(276) N-(1,3-dioxo-7-phenylisoindolin-4-yl)benzamide;
(277) N-(7-(2-methoxyphenyl)-1,3-dioxoisoindolin-4-yl)benzamide;
(278) N-(7-(2,3-dimethoxyphenyl)-1,3-dioxoisoindolin-4-yl)benzamide;
(279) 4-fluoro-N-(3-oxo-7-phenyl-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yl)benzamide;
(280) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide;
(281) N-(7-bromo-3-oxoisoindolin-4-yl)-4-((2-(dimethylamino)ethyl)amino)benzamide;
(282) N-(7-bromo-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide;
(283) N-(7-bromo-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(284) N-(7-bromo-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide;
(285) 4-((2-(azepan-1-yl)ethyl)amino)-N-(7-bromo-3-oxoisoindolin-4-yl)benzamide;
(286) N-(7-bromo-3-oxoisoindolin-4-yl)-4-((3-(dimethylamino)propyl)amino)benzamide;
(287) N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(288) N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((2-methoxyethyl)amino)benzamide;
(289) N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide;
(290) N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((2-morpholinoethyl)amino)benzamide;
(291) 4-((2-(dimethylamino)ethyl)amino)-N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)benzamide;
(292) N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((2-hydroxyethyl)amino)benzamide;
(293) 4-((2-(azepan-1-yl)ethyl)amino)-N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)benzamide;
(294) N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((2-(4-methylpiperazin-1-yl)ethyl)amino)benzamide;
(295) N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((3-(4-methylpiperazin-1-yl)propyl)amino)benzamide;
(296) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-morpholinopropyl)amino)benzamide;
(297) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-morpholinoethyl)amino)benzamide;
(298) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide;
(299) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(300) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-methoxyethyl)amino)benzamide;
(301) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(dimethylamino)ethyl)amino)benzamide;
(302) N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide;
(303) N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide hydrochloride;
(304) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide hydrochloride;
(305) 4-((2-(dimethylamino)ethyl)amino)-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(306) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-(dimethylamino)propyl)amino)benzamide;
(307) N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide;
(308) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide;
(309) 2-methyl-N-(3-oxo-7-phenylisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(310) 4-((3-methoxypropyl)amino)-N-(7-(2-methoxypyridin-3-yl)-3-oxoisoindolin-4-yl)benzamide;
(311) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-hydroxyethyl)amino)benzamide;
(312) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-morpholinobenzamide;
(313) N-(7-(3-fluoro-2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(314) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(4-methylpiperazin-1-yl)ethyl)amino)benzamide;
(315) 4-((2-aminoethyl)amino)-N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(316) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-(4-methylpiperazin-1-yl)propyl)amino)benzamide;
(317) N-(3-oxo-7-phenylisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(318) N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(319) 4-(4-methylpiperazin-1-yl)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(320) 4-morpholino-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(321) 4-((2-methoxyethyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(322) 4-((2-morpholinoethyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(323) N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-morpholinobenzamide;
(324) 4-((2-methoxyethyl)amino)-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(325) N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-(4-methylpiperazin-1-yl)benzamide;
(326) N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-morpholinoethyl)amino)benzamide;
(327) 4-((3-morpholinopropyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(328) N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-morpholinopropyl)amino)benzamide;
(329) 4-((3-(4-methylpiperazin-1-yl)propyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(330) N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-(4-methylpiperazin-1-yl)propyl)amino)benzamide;
(331) 4-((3-methoxypropyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(332) N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-methoxypropyl)amino)benzamide;
(333) N-(3-oxo-7-phenylisoindolin-4-yl)-4-((thiophen-2-ylmethyl)amino)benzamide;
(334) N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((thiophen-2-ylmethyl)amino)benzamide;
(335) 4-((3-(dimethylamino)propyl)amino)-N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)benzamide;
(336) N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((3-methoxypropyl)amino)benzamide;
(337) N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((3-morpholinopropyl)amino)benzamide;
(338) N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide;
(339) N-(7-(furan-2-yl)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide;
(340) 4-(4-aminopiperidin-1-yl)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(341) N-(7-(benzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)-4-((2-(dimethylamino)ethyl)amino)benzamide;
(342) N-(7-(benzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide;
(343) N-(7-(benzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide;
(344) 4-((2-(azepan-1-yl)ethyl)amino)-N-(7-(benzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)benzamide;
(345) 4-(2-morpholinoethoxy)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(346) N-(3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(347) N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)-4-(2-morpholinoethoxy)benzamide;
(348) N-(7-(3-amino-2-hydroxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-morpholinoethyl)amino)benzamide;
(349) 4-((2-(azepan-1-yl)ethyl)amino)-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(350) 4-((2-(azepan-1-yl)ethyl)amino)-N-(7-(2,3-dimethoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(351) 4-((3-(dimethylamino)propyl)amino)-N-(7-(2-hydroxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(352) 4-((2-hydroxyethyl)amino)-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(353) 4-((2-hydroxyethyl)amino)-N-(7-(2-hydroxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(354) 4-((3-hydroxypropyl)amino)-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(355) N-(7-(2-hydroxyphenyl)-3-oxoisoindolin-4-yl)-4-((3-hydroxypropyl)amino)benzamide;
(356) 4-((4-hydroxybutyl)amino)-N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(357) 4-((4-hydroxybutyl)amino)-N-(7-(2-hydroxyphenyl)-3-oxoisoindolin-4-yl)benzamide;
(358) 4-(methyl(2-(methylamino)ethyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(359) N-(7-(2,3-difluorophenyl)-3-oxoisoindolin-4-yl)-4-((2-morpholinoethyl)amino)benzamide;
(360) N-(3-oxo-7-phenylisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide;
(361) N-(7-(2-methoxyphenyl)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide;
(362) 4-((2-(dimethylamino)ethyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(363) N-(3-oxo-7-phenylisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide;
(364) N-(7-(2,3-difluorophenyl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(365) N-(7-(2,3-difluorophenyl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide hydrochloride;
(366) N-(7-(2,3-difluorophenyl)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide hydrochloride;
(367) N-(7-(2,3-difluorophenyl)-3-oxoisoindolin-4-yl)-4-((2-(dimethylamino)ethyl)amino)benzamide;
(368) N-(7-(2,3-difluorophenyl)-3-oxoisoindolin-4-yl)-4-((3-(dimethylamino)propyl)amino)benzamide;
(369) 4-((2-(azepan-1-yl)ethyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(370) N-(3-oxo-7-phenylisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide;
(371) 4-((2-hydroxyethyl)amino)-N-(3-oxo-7-(thiophen-2-yl)isoindolin-4-yl)benzamide;
(372) 4-((2-methoxyethyl)amino)-N-(3-oxo-7-(thiophen-2-yl)isoindolin-4-yl)benzamide;
(373) 4-((2-(dimethylamino)ethyl)amino)-N-(3-oxo-7-(thiophen-2-yl)isoindolin-4-yl)benzamide;
(374) N-(3-oxo-7-(thiophen-2-yl)isoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide;
(375) 4-((2-morpholinoethyl)amino)-N-(3-oxo-7-(thiophen-2-yl)isoindolin-4-yl)benzamide;
(376) N-(7-(benzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(377) N-(7-(2-methylbenzo[d]oxazol-7-yl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(378) 4-((2-(4-methylpiperazin-1-yl)ethyl)amino)-N-(3-oxo-7-(thiophen-2-yl)isoindolin-4-yl)benzamide;
(379) 4-((2-(4-methylpiperazin-1-yl)ethyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(380) 4-((2-hydroxyethyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(381) 4-((3-(dimethylamino)propyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(382) 4-((3-hydroxypropyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(383) 4-((4-hydroxybutyl)amino)-N-(3-oxo-7-phenylisoindolin-4-yl)benzamide;
(384) N-(7-(benzofuran-2-yl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(385) N-(3-oxo-7-(quinolin-6-yl)isoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(386) N-(3-oxo-7-(quinolin-5-yl)isoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(387) N-(3-oxo-7-(quinolin-4-yl)isoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(388) 7-(4-fluorobenzamido)-1-oxoisoindoline-4-carboxylic acid;
(389) 7-(4-fluorobenzamido)-N-methyl-1-oxoisoindoline-4-carboxamide;
(390) N-methyl-1-oxo-7-(4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamido)isoindoline-4-carboxamide;
(391) 4-fluoro-N-(3-oxo-7-(pyrrolidine-1-carbonyl)isoindolin-4-yl)benzamide;
(392) N-(3-oxo-7-(pyrrolidine-1-carbonyl)isoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(393) 4-fluoro-N-(7-(2-hydroxypropan-2-yl)-3-oxoisoindolin-4-yl)benzamide;
(394) N-(7-(2-hydroxypropan-2-yl)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(395) N-(7-cyano-3-oxoisoindolin-4-yl)-4-fluorobenzamide;
(396) 4-fluoro-N-(7-hydroxy-3-oxoisoindolin-4-yl)benzamide;
(397) 4-acetamido-N-(1-oxo-5-phenyl-1,2,3,4-tetrahydroisoquinolin-8-yl)benzamide;
(398) N-(1-oxo-5-phenyl-1,2,3,4-tetrahydroisoquinolin-8-yl)benzamide;
(399) N-(1-oxo-5-phenyl-1,2,3,4-tetrahydroisoquinolin-8-yl)furan-2-carboxamide;
(400) N-(5-(2,3-dimethoxyphenyl)-1-oxo-1,2,3,4-tetrahydroisoquinolin-8-yl)-4-fluorobenzamide;
(401) N-(1-oxo-5-phenyl-1,2,3,4-tetrahydroisoquinolin-8-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(402) N-(5-(2-methoxyphenyl)-1-oxo-1,2,3,4-tetrahydroisoquinolin-8-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(403) N-(5-bromo-1-oxo-1,2,3,4-tetrahydroisoquinolin-8-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(404) 4-fluoro-N-(3-oxo-7-(phenylthio)isoindolin-4-yl)benzamide;
(405) N-(1-oxo-5-(phenylthio)-1,2,3,4-tetrahydroisoquinolin-8-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(406) N-(3-oxo-7-(phenylsulfonyl)isoindolin-4-yl)benzamide;
(407) N-(3-oxo-7-(phenylthio)isoindolin-4-yl)benzamide;
(408) 4-fluoro-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
(409) N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
(410) N-(7-((2-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)benzamide;
(411) N-(3-oxo-7-(o-tolylamino)isoindolin-4-yl)benzamide;
(412) N-(3-oxo-7-(p-tolylamino)isoindolin-4-yl)benzamide;
(413) N-(7-((2-fluorophenyl)amino)-3-oxoisoindolin-4-yl)benzamide;
(414) N-(7-((4-fluorophenyl)amino)-3-oxoisoindolin-4-yl)benzamide;
(415) N-(7-((3-fluorophenyl)amino)-3-oxoisoindolin-4-yl)benzamide;
(416) N-(7-((4-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)benzamide;
(417) 4-methyl-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
(418) N-(7-((3-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-fluorobenzamide;
(419) N-(7-((2-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-fluorobenzamide;
(420) 2-fluoro-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
(421) 3-fluoro-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
(422) N-(7-((2,3-dimethoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-fluorobenzamide;
(423) N-(7-((3,5-bis(trifluoromethyl)phenyl)amino)-3-oxoisoindolin-4-yl)-4-fluorobenzamide;
(424) N-(7-((2,3-dimethylphenyl)amino)-3-oxoisoindolin-4-yl)-4-fluorobenzamide;
(425) 4-fluoro-N-(7-((2-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)benzamide;
(426) 4-fluoro-N-(3-oxo-7-(o-tolylamino)isoindolin-4-yl)benzamide;
(427) 4-fluoro-N-(3-oxo-7-(pyridin-3-ylamino)isoindolin-4-yl)benzamide;
(428) 4-fluoro-N-(3-oxo-7-(pyridin-2-ylamino)isoindolin-4-yl)benzamide;
(429) 4-fluoro-N-(3-oxo-7-(pyrazin-2-ylamino)isoindolin-4-yl)benzamide;
(430) 4-fluoro-N-(7-((l-methyl-1H-pyrazol-4-yl)amino)-3-oxoisoindolin-4-yl)benzamide;
(431) N-(7-((3-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)benzamide;
(432) 2-methoxy-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
(433) 4-methoxy-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
(434) 3-methoxy-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
(435) 4-acetamido-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
(436) N-(3-oxo-7-(m-tolylamino)isoindolin-4-yl)benzamide;
(437) N-(7-((1H-pyrazol-3-yl)amino)-3-oxoisoindolin-4-yl)-4-fluorobenzamide;
(438) N-(3-oxo-7-(phenylamino)isoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(439) N-(3-oxo-7-(phenylamino)isoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide;
(440) N-(3-oxo-7-(phenylamino)isoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide hydrochloride;
(441) 4-((2-(dimethylamino)ethyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
(442) 4-((2-morpholinoethyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
(443) 4-((2-(4-methylpiperazin-1-yl)ethyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
(444) 4-((2-methoxyethyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
(445) N-(7-((3-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(446) N-(7-((3-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide;
(447) N-(7-((3-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide;
(448) N-(7-((3-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide;
(449) N-(3-oxo-7-(m-tolylamino)isoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(450) N-(3-oxo-7-(m-tolylamino)isoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide;
(451) N-(3-oxo-7-(m-tolylamino)isoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide;
(452) N-(3-oxo-7-(m-tolylamino)isoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide;
(453) N-(7-((2-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(454) N-(7-((2-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide;
(455) N-(7-((3-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(456) N-(7-((3-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide;
(457) N-(7-((3-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide;
(458) N-(7-((3-chlorophenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide;
(459) N-(3-oxo-7-(phenylamino)isoindolin-4-yl)-4-((3-(2-oxopyrrolidin-1-yl)propyl)amino)benzamide;
(460) 4-((3-(dimethylamino)propyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
(461) 4-((3-morpholinopropyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
(462) N-(3-oxo-7-(phenylamino)isoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide;
(463) 4-((3-(4-methylpiperazin-1-yl)propyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
(464) 4-((3-hydroxypropyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
(465) N-(7-((3,5-bis(trifluoromethyl)phenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(466) N-(7-((3,5-bis(trifluoromethyl)phenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide;
(467) N-(7-((3,5-bis(trifluoromethyl)phenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide;
(468) N-(7-((3,5-bis(trifluoromethyl)phenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide;
(469) N-(7-((2,3-dimethylphenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(470) N-(7-((2,3-dimethylphenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide;
(471) N-(7-((2,3-dimethylphenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide;
(472) N-(7-((2,3-dimethylphenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide;
(473) N-(3-oxo-7-(o-tolylamino)isoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(474) N-(7-((2-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(475) N-(7-((2-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide;
(476) N-(3-oxo-7-(o-tolylamino)isoindolin-4-yl)-4-((3-(pyrrolidin-1-yl)propyl)amino)benzamide;
(477) N-(7-((2-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide;
(478) N-(7-((2-methoxyphenyl)amino)-3-oxoisoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide;
(479) N-(3-oxo-7-(phenylamino)isoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide;
(480) N-(3-oxo-7-(phenylamino)isoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide hydrochloride;
(481) 4-((2-aminoethyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
(482) N-(3-oxo-7-(o-tolylamino)isoindolin-4-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide;
(483) N-(3-oxo-7-(o-tolylamino)isoindolin-4-yl)-4-((3-(piperidin-1-yl)propyl)amino)benzamide;
(484) 4-((4-hydroxybutyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
(485) 4-((2-acetamidoethyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
(486) 4-((3-aminopropyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
(487) 4-((2-hydroxyethyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
(488) 4-((2-hydroxy-3-(piperidin-1-yl)propyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
(489) (S)-4-((2-hydroxy-3-(piperidin-1-yl)propyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
(490) (R)-4-((2-hydroxy-3-(piperidin-1-yl)propyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide;
(491) 4-(4-aminopiperidin-1-yl)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide; and
(492) 4-((2-(azepan-1-yl)ethyl)amino)-N-(3-oxo-7-(phenylamino)isoindolin-4-yl)benzamide, and
a pharmaceutically acceptable salt, a hydrate, and a solvate thereof.
15. A pharmaceutical composition for the prevention or treatment of cancer, which comprises the compound according to claim 1 and one or more pharmaceutically acceptable additives.
16. A pharmaceutical composition for the prevention or treatment of cancer, which comprises the compound according to claim 2 and one or more pharmaceutically acceptable additives.
17. A pharmaceutical composition for the prevention or treatment of cancer, which comprises the compound according to claim 3 and one or more pharmaceutically acceptable additives.
18. A pharmaceutical composition for the prevention or treatment of cancer, which comprises the compound according to claim 4 and one or more pharmaceutically acceptable additives.
19. A pharmaceutical composition for the prevention or treatment of cancer, which comprises the compound according to claim 5 and one or more pharmaceutically acceptable additives.
20. A pharmaceutical composition for the prevention or treatment of cancer, which comprises the compound according to claim 6 and one or more pharmaceutically acceptable additives.
21. A pharmaceutical composition for the prevention or treatment of cancer, which comprises the compound according to claim 7 and one or more pharmaceutically acceptable additives.
22. A pharmaceutical composition for the prevention or treatment of cancer, which comprises the compound according to claim 8 and one or more pharmaceutically acceptable additives.
23. A pharmaceutical composition for the prevention or treatment of cancer, which comprises the compound according to claim 9 and one or more pharmaceutically acceptable additives.
24. A pharmaceutical composition for the prevention or treatment of cancer, which comprises the compound according to claim 10 and one or more pharmaceutically acceptable additives.
25. A pharmaceutical composition for the prevention or treatment of cancer, which comprises the compound according to claim 11 and one or more pharmaceutically acceptable additives.
26. A pharmaceutical composition for the prevention or treatment of cancer, which comprises the compound according to claim 12 and one or more pharmaceutically acceptable additives.
27. A pharmaceutical composition for the prevention or treatment of cancer, which comprises the compound according to claim 13 and one or more pharmaceutically acceptable additives.
28. A pharmaceutical composition for the prevention or treatment of cancer, which comprises the compound according to claim 14 and one or more pharmaceutically acceptable additives.
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